The clinical and economic impact of heart failure (HF) is well documented. It affects 22 million people worldwide, occurs in at least 2% of the Western adult population and is a progressive condition with high morbidity and mortality rates, placing a significant burden on healthcare resources.3 One of the keys to reducing the clinical and economic impact of HF is accurate and early diagnosis of left ventricular systolic dysfunction (LVSD). This is essential for both successfully addressing underlying diseases or causes and selecting appropriate therapies.1
The recognition by the American College of Cardiology and American Heart Association of transthoracic echocardiography as a first-line diagnostic test in the evaluation of patients with HF and the growing clinical acceptance of therapeutic techniques such as cardiac resynchronisation therapy (CRT) have fuelled interest in new echocardiographic techniques, such as live three-dimensional (3-D) imaging, tissue Doppler imaging (TDI) and associated analysis tools for dynamically assessing regional volumes and differences in timing of contraction. Of these approaches, TDI is well documented, but is limited by technical limitations such as angle dependence, particularly in dilated ventricles. A new technology for the analysis of tissue motion based on the underlying speckle patterns in tissue backscatter has recently been evaluated as an alternative to TDI for assessment of segmental contraction timing and regional function. This method – known as speckle tracking or tissue motion quantification (TMQ) – offers several unique advantages over other two-dimensional (2-D) investigation tools. These advantages include freedom from angle dependence and the ability to simultaneously interrogate multiple motion parameters (such as radial and longitudinal contraction). This article evaluates the potential of this new technology alongside more established methods for improving accuracy and reproducibility in HF assessment and monitoring.
Aetiology and Prognosis in Heart Failure
HF associated with LVSD is characterised by progressive structural change in the left ventricle (LV), known as remodelling. As the disease progresses, myocyte hypertrophy and elongation give rise to LV dilatation and hypertrophy. In this situation, stroke volume is increased without an actual increase in ejection fraction (EF). This results in increased wall tension and impaired subendocardial myocardial perfusion, and may provoke ischaemia. As this dilatation progresses, separation of the valve leaflets can lead to mitral and tricuspid regurgitation. This may further diminish the cardiac output and increase end-systolic volumes and ventricular wall stress, leading to further dilation, pulmonary congestion and myocardial dysfunction. LV volumes and EF are therefore important prognostic indicators for morbidity and mortality in HF patients.8
Echocardiography in the Diagnosis and Monitoring of Heart Failure
Echocardiographic Analysis of Ejection Fraction
Measurement of EF typically uses manual planimetry of 2-D areas according to Simpson’s single-plane or bi-plane method of disks. This method can be time-consuming and has been shown to exhibit inaccuracies compared with the gold standard of magnetic resonance imaging (MRI).9 Chief sources of error derive from inconsistent acquisition methods, incorrect image plane selection and subjective boundary definition by readers. Variable image quality, particularly in technically difficult patients, may further exacerbate many of these inaccuracies. Imaging advances such as tissue harmonic imaging and, more recently, the use of homogenous, mono-crystal elements in transducer design (PureWaveCrystal Technology) have substantially improved the robustness of echocardiographic analysis in technically difficult patients. PureWaveCrystal technology in particular has provided a breakthrough in imaging fidelity, which is a pre-requisite for new technologies such as speckle tracking. Speckle tracking in tandem with PureWaveCrystal technology offers a promising solution for LV border tracking and automated EF/volume data. These technologies also provide access to new parameters for quantifying global LV function such as mitral annular displacement.
Another source of error in 2-D echocardiogram data lies in the geometric assumptions used in volume calculations. These limitations may be largely addressed with the use of full-volume 3-D data for retrospective selection of the true four- and two-chamber planes. Second-generation matrix transducers allow realtime acquisition of high-resolution 3-D volumes for analysis of global and regional volume data. This has important potential workflow and accuracy benefits: instead of striving to obtain correct 2-D image planes at the time of the scan, the operator may now acquire a single volume that may be analysed on-cart or off-cart using 3-D quantification (3-DQ) multiplanar reconstruction to provide access to any image planes.20,21 Further advances in 3-D analysis software now also allow assumption-free analysis of true volumes based on a robust voxel detection algorithm. Technologies that can significantly improve the speed, reproducibility and accuracy of EF measurements can be divided into four categories based on the benefits they offer and are summarised in Table 1.
Two-dimensional Quantification Semi-automatic Ejection Fraction and Volume Analysis
Acoustic quantification (AQ) and colour kinesis (CK) have for several years provided a promising approach for realtime semi-automated EF and volumetric measurements. CK provides a qualitative display of wall displacement in colour-coded time intervals to reduce subjectivity in regional wall motion assessment, while AQ generates dynamic volume data leading to improved reproducibility and rapidity of EF and LV volume determination. In Philips QLAB software, which is available both on-cart and as an off-cart tool, it is now possible to apply speckle tracking for AQ border tracking. This means that, instead of detecting a new border in every frame, the software is able to follow speckle patterns in the 2-D image backscatter for highly robust, dynamic tracking performance (see Figure 1).
Speckle-tracking Technology
The introduction of live 3-D was a landmark in cardiovascular ultrasound, introducing the concept of a ‘single acquisition scan’ containing all of the data needed for retrospective analysis, interrogation and clinical decision-making. In a similar vein, TMQ speckle analysis of 2-D image data provides the possibility for ‘any-angle’ interrogation of motion and deformation and multiple functional indices from any standard 2-D acquisition. Before the advent of speckle tracking, angle-independent assessment of LV deformation and rotation was possible only with MRI tagging.
Speckle is a marker/pattern/fingerprint that allows ultrasound post-processing technology to monitor and follow the underlying tissue movement from frame to frame (see Figure 2). The technique searches within a specified region of interest for correlation of ultrasound speckle patterns within image ‘blocks’ in the backscattered tissue signals. It is then possible to describe 2-D tissue motion by tracking the frame-to-frame movement of the associated speckle patterns.
One of the key determinates of speckle-tracking performance is the information content and fidelity of ultrasound images. Because of this, TMQ speckle tracking is reserved for images acquired with PureWaveCrystal transducers, as they offer both superior clarity and extended bandwidth, allowing recognition of a wider range of frequency-specific tissue signatures. As well as providing more robust tracking for established techniques such as AQ, TMQ speckle tracking offers an alternative approach for techniques such as TDI for velocity, strain and strain-rate imaging, overcoming many of the problems traditionally associated with angle dependence. The great advantage of this lies in the possibility of simultaneously interrogating radial and circumferential or longitudinal motion from the same acquired loop. Using Doppler methods, it is essential to carry out at least two separate acquisitions to perform this type of investigation (see Figure 2).
Speckle offers further advantages over Doppler methods, which assume that the same region of tissue is sampled throughout the heart cycle. However, this assumption cannot be proved unless speckle tracking is used. TMQ speckle tracking may therefore be used as an alternative or complementary tool for applications such as CRT/synchronicity assessment. A TDI versus TMQ speckle tracking comparison is summarised in Table 2.
TMQ speckle tracking also allows access to new quantitative parameters such as tricuspid or mitral annular displacement (TMAD). Attempts to characterise global function based on the annular or atrioventricular (AV) plane motion have been documented for well over a decade.20 Using QLAB software, it has been possible to qualitatively assess MAD since 2004, when Philips introduced a version of speckle-tracking technology with mitral annular CK. This capability has now been extended to allow plotting of time versus vertical displacement curves that have been correlated with global LV function in a study by Dr Lang.20 This study demonstrates the potential of TMAD to provide a useful alternative to the measurement of EF as the key indicator of global systolic and diastolic function (see Figures 3a and 3b).
This capability is also available on bi-plane acquisitions using the xPlane capability of xMatrix live 3-D transducers. This allows full interrogation of the septum, anterior, lateral and inferior (SALI) portions of the annular ring in a single acquisition (see Figure 3c) and promises to provide particular clinical and workflow benefits in stress echocardiogram investigations. The same technique may be applied on the tricuspid valve for interrogation of RV function. Analysis of vertical displacement need not be confined to the mitral ring, but may be extended to include virtually any number of chords at multiple levels within the LV or RV. Figure 3d illustrates this concept, showing the characteristic motion gradient from base to apex.
TMQ is presently a 2-D imaging application, but its greatest potential may lie with 3-D datasets, allowing true characterisation of the complex components of cardiac motion in a single acquisition. This promises to be an important area for future scanner and software design.
Tissue Motion Quantification Speckle versus Tissue Doppler Imaging for Cardiac Resynchronisation Therapy Assessment
In approximately 30% of patients with heart failure, an intraventricular conduction delay or bundle branch block causes the ventricles to beat in an asynchronous fashion. This can greatly reduce the efficiency of the already damaged ventricle. CRT using bi-ventricular pacing is a new technique that can improve the co-ordination of contraction and thereby relieve heart failure symptoms and effects.11,13 Recent research has shown that evidence of intraventricular mechanical dyssynchrony is an important independent predictor of likely responders to CRT. This evidence can be readily obtained using regional volume curves acquired from 3-D datasets or regional tissue Doppler velocity curves to derive an index of dyssynchrony.
Yu et al.11,13 analysed time to peak systolic velocity (TPSV) using 12 segments (basal and mid for each wall in three apical views). Using this approach, intraventricular dyssynchrony may be inferred from the maximum difference (MaxDiff) between two regions (e.g. basal septum and basal lateral wall) or the standard deviation of 12 segments (SD index). The strain quantification (SQ) plug-in for QLAB software provides the possibility for fast comparison of TPSV between four or more segments per apical view to provide 12 or more segments in total.
The same approach may be adopted either on-cart or off-cart using TMQ speckle software. TMQ offers the advantage of automatic segmentation of the LV into seven segments per apical view with less dependence on angle and no need to adjust m-lines or reactive oxygen intermediates (ROIs) to track the myocardium as it moves (see Figure 4). Evidence from the author’s own lab suggests that TMQ-derived SD indices correlate well with values based on TDI data.
Three-dimensional Approach for Cardiac Resynchronisation Therapy Assessment
The image acquisition and analysis tools reviewed so far provide the promise of improved inter- and intra-observer variability, but do not address the important issue of geometric assumptions needed to infer overall cardiac function from measurements taken in 2-D imaging planes. The use of 3-D volume data for evaluation of intra-ventricular mechanical dyssynchrony/CRT assessment is based on the regional time to minimum systolic volume (TMSV) measured from onset of QRS to minimum value of regional volume/time curves.14 Intraventricular dyssynchrony may be inferred from maximum difference between two regions (e.g. basal septum and basal lateral wall) or SD standard deviation of up to 17 regional volumes (see Figure 5). The addition of speckle tracking to 3-D analysis would be a vital complement to the use of time–volume curves and comparison of TMSV. For the first time, it would be possible to obtain detailed, angle-independent motion parameters in any plane to corroborate the mechanical evidence based on regional volume data.
Conclusion
Transthoracic echocardiography provides vital information for diagnosis, prognosis and choice of therapies in heart failure. Reproducible, accurate echocardiographic data rely on high-quality images as well as advanced analysis tools designed to improve accuracy, reduce operator dependence and remove geometric assumptions. With the growing acceptance of CRT as a therapeutic option, new echocardiographic imaging modalities such as TMQ 2-D speckle tracking, live 3-D imaging and specialised analysis tools for dynamically assessing regional function and differences in timing of contraction promise to play an expanding role in the management of HF. As TMQ speckle technology evolves, the potential for its implementation as a 3-D tool promises to greatly expand our ability to rapidly and accurately quantify global and regional function and gain further insight into the complex mechanics of LV contraction.