Clinical Benefits of New Echocardiographic Methods

1. Introduction

Congenital heart diseases (CHD) are highly variable, ranging from simple to complex lesions. Therefore, pediatric echocardiography faces different challenges, especially in demonstrating complex anatomy and assessing myocardial function in ventricles with variable morphology [1]. At the same time, there is a desire to detect early changes in ventricular function in cardiac patients as well as in patients with systemic diseases potentially affecting the heart. Furthermore, bedside techniques are increasingly used in clinical medicine, which is also seen in pediatric echocardiography. Consequently, the development of new methods or the upgrade of existing ultrasound techniques is urgently needed.

Recent advances in pediatric echocardiography include functional imaging, myocardial deformation imaging, and 3D echocardiography. Advances in ultrasound techniques, especially in pediatric probes, allow imaging with high temporal and spatial resolution, which opens a new perspective on the mechanics and function of the myocardium. 3D echocardiography can help understand complex anatomy with associated functional changes, which is valuable for appropriate intervention planning. For pediatric cardiac patients, a highly variable ventricular morphology is typical, therefore, assessment of myocardial function may be challenging, especially assessment of right ventricular function and function of a single ventricle. Deformation imaging with strain and strain-rate quantification enables quantitative assessment of myocardial function independent of underlying morphology [1, 2]. Strain imaging also enables detecting minimal changes in the global and regional systolic function of the ventricles and allows recognition of the preclinical stage of different diseases affecting the heart [3].

Functional echocardiography has become increasingly useful in everyday clinical practice; nowadays it plays a central role in understanding and managing hemodynamics in critically ill patients [4]. Functional echocardiography facilitates real-time evaluation of cardiac performance, identifying the nature of cardiovascular compromise, guiding therapeutic decisions, and monitoring response to treatment [5]. Namely, early detection of cardiac dysfunction may help to choose an appropriate inotropic or vasopressor support. Good collaboration with pediatric cardiologists taking care of the patient is essential in the performance and interpretation of functional echocardiography [6].

2. Functional echocardiography

Bedside functional echocardiography provides physiological information and is a useful real-time noninvasive method among other monitoring tools for critically ill children. It is being increasingly used in making therapeutic clinical decisions and assessing response to treatment in unstable patients in the intensive and emergency units [7].

Functional echocardiography allows bedside use of cardiac ultrasound that brings fast and efficient investigation and recognition of the key hemodynamic changes, an assessment of cardiac function, pulmonary hypertension, pericardial effusion, and evaluation of the shunts. It provides insights into pathophysiology that leads to significant hemodynamic instability, and in addition, therapeutic interventions could be better planned and targeted. It also enables monitoring responses to treatment, which allows rapid therapeutic adjustments [7, 8, 9, 10].

Functional echocardiography is also called targeted echocardiography, point-of-care cardiac ultrasound, or clinician performed ultrasound. It is being used to assess preload, afterload, and cardiac contractility while choosing inotropic or fluid therapy [4, 7].

Functional echocardiography performed in the newborn differs significantly from that performed in older children, because of the increased risk of critical or significant CHD. Therefore, the first echocardiography performed on a newborn should be accurate and structured with sequential segmental analysis of the heart. The subsequent scans can be functional, focused, or targeted to address specific clinical questions [7, 11, 12, 13].

Table 1 summarizes the recommendations for the practice of functional echocardiography including neonatologist-performed echocardiography.

Clinical benefits of functional echocardiography are well seen in patients with hypotension and shock, which are common conditions in critically ill children, both likely to have high mortality. Furthermore, echocardiography is crucial in identifying the underlying pathophysiology, evaluating hemodynamics, and managing the response to treatment in patients with shock [7, 14].

Information from functional echocardiography in conjunction with other clinical parameters and monitoring tools can be used in choosing fluid resuscitation therapy and appropriate inotropic, vasopressor, or vasodilator therapy [15, 16, 17]. Early recognition of increased pulmonary pressure may help in the early institution of pulmonary vasodilators, especially in neonates with pulmonary hypertension [7, 9, 11, 17].

Functional echocardiography offers the potential for novel insights into cardiovascular impairment. Specifically, whether the concern relates to preload, afterload, or myocardial contractility. Serial echocardiography evaluation to monitor treatment response may provide a better understanding of physiology and guide the duration of treatment, which minimizes drug exposure [11].

Assessment of volume status is usually made with inferior vena cava (IVC) size and collapsibility, which is also the method of choice to evaluate right heart filling pressure. This can be done easily in spontaneously breathing children, but some limitations exist in ventilated patients. In the presence of cardiogenic shock and increased right heart filling pressure, the IVC will appear dilated with no respiratory variation [15].

Qualitative estimation of the severity of pulmonary hypertension can be made by assessing the shape of the left ventricle and interventricular septum (IVS) motion, which is obtained from the parasternal short-axis view. With rising pulmonary artery pressure (PAP), the left ventricle begins to lose its circular shape and IVS starts to flatten, furthermore, paradoxical septal movement may occur in severe pulmonary hypertension [7, 9]. The shunt across the patent foramen ovale (PFO) is generally bidirectional in the presence of pulmonary hypertension but can sometimes be left-to-right even in the presence of severe pulmonary hypertension. An exclusively right-to-left shunt across the PFO is always abnormal and suggests elevated right heart filling pressure [6]. Direct assessment of the pulmonary artery pressures can be done by a peak velocity of the tricuspid insufficiency jet using the modified Bernoulli equation. The pulmonary artery systolic pressure (PASP) may be estimated by adding right atrial pressure to the peak systolic pressure gradient between the right ventricle and right atrium. The mean pulmonary artery pressure (MPAP) is assessed by using the peak diastolic velocity of the pulmonary regurgitation jet. The end-diastolic velocity of the pulmonary regurgitation jet is used to estimate diastolic pulmonary artery pressure (DPAP) [6, 7]. Functional echocardiography is useful in the initiation of vasodilator treatment (such as inhaled nitric oxide) and monitoring the response to treatment [6].

Pericardial effusion is a common condition in intensive care units; functional echocardiography allows easy diagnosis and timely echo-guided pericardiocentesis [18]. The hemodynamic effect of pericardial effusion does not depend solely on the amount of pericardial fluid. A large amount of pericardial fluid can be well tolerated when the fluid accumulates slowly. However, rapidly increasing pericardial effusion is more dangerous and may lead to cardiac tamponade. The main echocardiographic signs of cardiac tamponade are distended IVC with no respiratory variation, right atrial collapse at the end of diastole, right ventricular free wall collapse during diastole, and respiratory variation of Doppler mitral inflow for more than 10% and tricuspid inflow for more than 25% [7].

Patent ductus arteriosus (PDA) is an independent risk factor for intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia (BPD), and acute pulmonary hemorrhage [19, 20]. The hemodynamic significance of a PDA may not be directly related to the size of the PDA but depends upon the magnitude of the shunt and the ability of the myocardium to adapt to a left-to-right shunt [7, 20, 21, 22]. PDA causes pulmonary hyperperfusion and systemic hypoperfusion, which could be assessed with functional echocardiography. The duration of the shunt and the level of diastolic flow reversal in the descending aorta are good indicators of the significance of PDA and can be used for follow-up. An additional factor in assessing the PDA is pulmonary artery pressure, which can be monitored based on PDA Doppler velocity magnitudes. A low-pressure gradient between the aorta and pulmonary artery may be associated with pulmonary hypertension. Non-restrictive PDA has a low peak systolic velocity with a high systolic to diastolic velocity gradient, while restrictive shunt is characterized by a high peak systolic velocity and a low systolic to diastolic velocity gradient [21]. Functional echocardiography has also been reported to improve the outcomes in infants being treated for PDA, the impact of this echocardiographic method is still the subject of ongoing research [23, 24]. Furthermore, it has been found that the performance of bedside echocardiography reduces the number of indomethacin doses used for treating PDA [25, 26]. The introduction of a functional echocardiography screening program for hemodynamically significant PDA on day 3 of life with the targeted intervention was associated with a reduction of severe intraventricular hemorrhage and ventilation duration [25, 27]. Serial echocardiography was associated with earlier identification and treatment of PDA, lower rates of severe intraventricular hemorrhage, and reduced ventilator days [11, 25].

3. Myocardial deformation imaging

Conventional methods for assessment of regional and global ventricular function, such as fractional shortening and ejection fraction, are largely dependent on loading conditions and geometric assumptions [28, 29]. Myocardial deformation imaging has introduced a new global parameter of left ventricular longitudinal deformation GLS (global longitudinal strain), which has turned out to be more sensitive for early detection of myocardial impairment compared to conventional echocardiographic systolic function parameters. Myocardial deformation parameters have diagnostic as well as prognostic values in several cardiac diseases [3].

Recent developments in the assessment of ventricular function are the measurement of myocardial tissue Doppler velocities (tissue Doppler imaging, TDI) and deformation imaging (strain and strain-rate quantification). TDI has some advantages over traditional echocardiographic techniques in providing measurements of cardiac tissue movements [7, 30]. Myocardial deformation analysis is a quantitative technique that helps define a global and regional function of both ventricles. Tissue deformation is measured by cardiac strain, and there is an additional parameter called strain rate that defines the rate of myocardial deformation in time [7].

Compared to traditional methods that measure cardiac function mainly in the radial direction, strain imaging does not rely on geometric assumptions and can quantify function in the longitudinal, radial, and circumferential direction of motion. Therefore, regional as well as global ventricular function may be better estimated. Strain rate measures the extent of shortening of the myocardium in the longitudinal and circumferential directions and thickening in the radial direction. These newer methods of myocardial function assessment have already shown great promise in several areas of pediatric echocardiography, but their use in clinical practice is still limited by the lack of data from large patient cohorts [1].

Recently, two-dimensional (2D) and three-dimensional (3D) speckle-tracking echocardiography (STE) has been introduced as a new method to quantify myocardial strain [29]. STE tracks the motion of speckles within the scan volume, allowing a more complete and accurate assessment of myocardial deformation in all three spatial dimensions [29, 31]. Strain imaging is a promising method for assessing left ventricular function for diagnosis, prognosis, and risk stratification of various congenital and acquired heart diseases; it is also useful for monitoring treatment outcomes before and after medical, percutaneous, and surgical interventions [29].

Strain and strain rate can be measured either from tissue Doppler velocities or with speckle-tracking techniques together with final analysis at the workstation. It is necessary to be aware of the wide variability of the strain and strain rate measurements that depend on vendors, software packages, and echocardiographic laboratories, as shown in Table 2 [32, 33]. Broad clinical use of the strain is still limited due to the intervendor differences and related difficult comparison of the results, thus, standardization is urgently needed [1, 34]. Higher heart rates, especially in younger children, require higher frame rates, particularly for strain rate imaging; therefore, this aspect of use requires further development. Another challenge for the implementation of strain imaging in everyday clinical practice is the availability of reference values for different age groups of children [1, 35].

3D speckle-tracking provides a more comprehensive evaluation of ventricular mechanics from pyramidal 3D datasets. Furthermore, it enables also more precise mechanical activation mapping compared to 2D strain, by being maximum opposing wall delay and SD (standard deviation) still significantly correlated with similar 2D strain measurements. 3D loops of regional strain are color-coded and divided into 16 or 18 segments for time-strain curves. The results are presented in a 16- or 18-segment polar map with segmental systolic strain values displayed in the bull’s eye. GLS value is defined as the average peak longitudinal strain of the left ventricle [36, 37]. Future development and expansion of applications for 3D speckle tracking are anticipated.

Strain imaging has also been used to gain a greater understanding of the pathophysiology of cardiac ischemia and infarction, primary diseases of the myocardium, the effects of valvular disease on myocardial function, and understanding of diastolic function, as seen in Table 3. Strain imaging has also been used for heart failure patients undergoing cardiac resynchronization pacing therapy providing important quantitative information on the timing of mechanical activation. Strain imaging has become increasingly used for research purposes, in addition, it shows great potential for routine clinical practice in the light of the improved treatment of cardiovascular patients [37]. Therefore, deformation imaging also plays a role in the risk stratification of young individuals with a potentially increased risk for heart failure and sudden cardiac death [1, 38]. Strain imaging has also been used to help to differentiate between athlete’s heart and individuals with potential cardiomyopathy [1, 39]. While multiple studies have shown the usefulness of strain quantification for risk stratification in various diseases, such as arterial hypertension, diabetes mellitus, metabolic syndrome, chronic kidney disease, neuromuscular diseases, and others, the main limitation remains that strain values vary among methods, modalities, and software versions [40, 41, 42].

Ventricular morphology can be highly variable in CHD, and therefore traditional methods of assessment of ventricular function that rely on geometry are unreliable. Assessment of right ventricular function and evaluation of functional changes in patients with a single ventricle are particularly challenging. Assessment of regional function is also important in pediatric patients with coronary artery abnormalities [1]. Subtle impairment in myocardial function, detectable with strain imaging, can be used to identify asymptomatic patients who progress to require valve surgery, which improves timely planning of the appropriate treatment [43].

Due to geometric factors, strain imaging better reflects systolic function in patients with preserved ejection fraction (EF), which is also common in cardiomyopathies. Particularly, longitudinal shortening may vary in patients with cardiomyopathies significantly, as it has less effect on EF than circumferential shortening. Therefore, longitudinal shortening might potentially be a more sensitive marker of systolic dysfunction, which typically affects the subendocardial region first, and could be assessed with longitudinal strain [44]. Deformation parameters, especially global longitudinal strain, have better accuracy in detecting cardiac amyloidosis in patients with thickened hearts [45].

Strain imaging is a beneficial additional echocardiographic method in assessing the extent of the ischemic myocardium and ventricular function. Postsystolic shortening is an important feature of the ischemic myocardium as a marker of tissue viability, and when associated with systolic hypokinesis or akinesis, it indicates actively contracting myocardium. When combined with dyskinesis, however, postsystolic shortening seems to be a nonspecific marker of severe ischemia [46]. Semiautomated calculation of GLS is significantly related to all-cause mortality or heart failure in patients with myocardial infarction and left ventricular ejection fraction (LVEF) > 40% [47].

Strain imaging is effective in monitoring cardiac function in patients with the multisystem inflammatory syndrome in children (MIS-C), which occurs after COVID-19 infection. Patients with preserved LVEF in myocarditis within MIS-C had significantly lower GLS; furthermore, regional myocardial dysfunction may also be presented, as seen in Figure 1. Hence, even preserved EF patients show subtle changes in myocardial deformation, suggesting subclinical myocardial injury. During a follow-up of the patients with MIS-C, there was a good recovery of systolic function but the persistence of diastolic dysfunction [48, 49]. Speckle-tracking imaging can help in the diagnosis of acute myocarditis when cardiovascular magnetic resonance (CMR) is not readily available or cannot be performed. There is a good correlation between speckle-tracking imaging-based LVEF, global strain and magnetic resonance imaging (MRI) calculated LVEF [50].

Segmental strain curves in a four-chamber view (top left), two-chamber view (top right), three-chamber view/APLAX—apical long-axis view (bottom left), and 18-segment model or bull’s eye (bottom right). The numbers in segments in the bull’s eye are the peak longitudinal strain values in systole. The calculated value of global longitudinal strain (GLS) is −13.3%. Systolic values of the longitudinal strain are reduced in basal and mid-cavity segments of the anterior and lateral wall (blue color).

The recognition of early left ventricular dysfunction in cancer patients after cardiotoxic therapy may allow the identification of individuals at risk of future heart failure, allowing targeted monitoring and possibly institution of potential therapies such as angiotensin-converting enzyme inhibitors. The potential of strain imaging to prevent future cardiac toxicity by modulating cancer therapy and the institution of cardiac protective therapy is promising [51, 52].

GLS is the preferred indicator of left ventricular global systolic function. Strain measurements have proven to be more reproducible than LVEF due to minor dependency on segmental variability than LVEF calculations. Additionally, strain measurements should be obtained with the same analysis system and software version [42, 53, 54, 55].

Strain imaging is designed for the echocardiographic assessment of regional and global myocardial function, and has been well studied in the adult population, however, its use in pediatrics appears to be limited [56, 57, 58]. The duration of the investigation and the need to perform post-processing are major barriers to the more widespread implementation of the strain. Fully automated analysis with algorithms validated in the pediatric population may remove this problem [58].

4. 3D echocardiography

3D echocardiography (3DE) allows imaging and analysis of cardiovascular structures as they move in time and space, which enables the creation of 4D datasets (3D in real-time). Real-time 3DE is a major innovation in the history of cardiovascular ultrasound [59].

3DE is increasingly used in patients with congenital heart disease, as it allows the visualization of lesions in three dimensions, with opportunities for increased appreciation of complex spatial relationships. Alternative imaging modalities such as CMR or computed tomography (CT) have, compared to 3DE, some disadvantages, such as expense, general anesthesia (CMR), or exposure to radiation (CT) [1].

Clinical benefits of 3DE are evident in three main areas: better visualization and understanding of the spatial relationships and 3D morphology of congenital heart defects; quantification of cardiac mass and volumes; planning and guiding therapeutic interventions, as seen in Table 4 [1, 60].

However, 3DE scanning modalities that use the ECG for gating, and then collect the data acquired over several heartbeats are often problematic in younger patients, as there is a large potential for movement artifact, especially with higher respiratory rates. The main shortcomings of 3D imaging have been the lower spatial and temporal resolution compared with 2D imaging, and the requirement for offline analysis [1, 60].

Compared to cross-sectional imaging methods 3DE does not use the same geometric assumptions, which allows a more accurate assessment of the cardiac function. At the same time, with better visualization also comes a better understanding of the anatomy of CHD, such as atrial and ventricular septal defects, atrioventricular (AV) septal defects, and atrioventricular valve or outflow tract abnormalities. In addition, 3DE enables better volumetric assessment of cardiac chambers in patients with borderline sized ventricles, it can also work as an important diagnostic tool for cardiac mass. 3DE findings correlate well with surgical findings, and can significantly improve the planning of therapeutic interventions, sometimes may also reduce the operative time [1].

3DE offers the additional advantage to estimate the AV valve regurgitant volume, the mechanism, and the origin of regurgitation with clear visualization of the valves, which makes 3DE an ideal imaging modality to evaluate these structures and plan interventions [61, 62, 63, 64]. 3DE is also a promising modality for 3D printing of AV valves, structures that are largely missing from cardiac models using exclusively MRI or CT data [64, 65, 66].

The 3DE and 4DE with spatiotemporal image correlation allow obtaining fetal cardiac volumes and their static and real-time analysis [67], and multiple two-dimensional images are stacked one behind the other to create a volume dataset [68, 69, 70]. 4DE is used mainly in the field of fetal echocardiography for the dynamic assessment of fetal cardiac structures and large vessels. The main challenge of fetal echocardiography is still a profound understanding of the spatial relationships and connections of the cardiac structures and great vessels, which 4DE overcomes with more accurate anatomic information. Although traditional 2D echocardiography is the basic modality for prenatal diagnosis of CHD, 3DE and 4DE should be considered as very useful additions [71].

5. Conclusions

Recently, the focus of the development of pediatric echocardiography has shifted toward accurate assessment of myocardial function and precise presentation of cardiac morphology. As in other areas of ultrasound examinations, there is an increasing need for bedside targeted echocardiography that provides fast answers to major clinical challenges. Therefore, some echocardiographic methods becoming increasingly useful, such as functional echocardiography, cardiac deformation imaging, and 3D echocardiography.

Functional echocardiography enables real-time evaluation of cardiac performance, identifying the nature of cardiovascular compromise, guiding therapeutic decisions, and monitoring response to treatment. An additional advantage of functional echocardiography is the noninvasiveness of the method. The decision-making process is easier with further information provided by targeted echocardiography, which also reduces a substantial proportion of interventions. Standardized training and close collaboration with pediatric cardiologists are essential for ensuring patients’ safety and quality of examination, especially in neonatal units where the risk of a critical or major CHD is higher compared to older children. Future research should address short-term cardiovascular effects and long-term outcomes of functional echocardiography.

Myocardial deformation imaging may be beneficial for the detection of early ventricular dysfunction, especially where classical methods are unreliable. A better understanding of patterns of dysfunction may help clinicians to identify causative factors for global and regional ventricular dysfunction. Patients with progressive heart disease or systemic disease affecting the heart may be identified and treated timely. Furthermore, closer monitoring of the effects of therapy is also an important advantage of myocardial deformation. New methods of myocardial function assessment have already shown great promise in several areas of pediatric echocardiography, but the main limitation remains that strain values vary among methods, modalities, and software versions. Further investigation is warranted for the potential clinical applications in a pediatric population, especially in defining the normal range and maturational changes in strain.

3DE is a very promising and topical new echocardiographic method; recently, it has become more popular in patients with CHD, as it allows the visualization of defects in three dimensions, with opportunities for increased appreciation of complex spatial relationships. A current limitation of 3DE is a restriction of spatial and temporal resolution. Based on 3D modeling, virtual surgery may even be possible, to optimize device design for individual patients, or to determine the optimal surgical technique. In a near future, we are likely to see increased use of 3DE during transcatheter interventions and heart surgeries.

Conflict of interest

The authors declare no conflict of interest.