Clinical applications of speckle tracking
Novel echocardiographic techniques allow the assessment of myocardial strain. Strain can measure myocardial deformation which is an intrinsic mechanical property of the myocardium. Assessments of strain reflect myocardial systolic function more directly than conventional cavity-based echocardiographic parameters. The traditional volume measurement-based echocardiographic parameters are indirect means of assessing myocardial function, and are insensitive to early changes in myocardial function. The most commonly used echocardiographic parameter to evaluate ventricular function is ejection fraction, however, its measurement presents a number of challenges related assumptions of ventricular geometry, expertise and is limited to assessing changes in ventricular cavity size during the cardiac cycle.
The occurrence of myocardial disease can precede structural myocardial changes shown by traditional imaging techniques. Accurate assessment of myocardial function is therefore particularly important in patients with potential to develop serious cardiac disease. Myocardial strain by 2D speckle tracking echocardiography has demonstrated to be a sensitive tool for assessing ventricular function in early myocardial disease.
Normal myocardial strain values
In healthy individuals, average peak systolic left ventricular longitudinal strain assessed by speckle tracking technique is in the range of -18 - -20%, systolic circumferential strain is 20 - -22% and radial systolic strains >+40%, respectively.
Due to variance between strain values between vendors, a joint workgroup of the American Society of Echocardiography (ASE), the European Association of Echocardiography (EAE) and representatives of all Medical Imaging vendors will work for a standardization of strain values from different scanners. The algorithms used by the different software packages are similar in terms of the speckle-tracking analysis, which is based on a block-matching approach of the speckle patterns within the myocardium, however, the strain calculation formulas used are somewhat varying. There are presently ongoing trials with the different scanners using the same formula for strain calculations.
Early detection of reduced myocardial function
Myocardial function in non-ischemic cardiomyopathy
Strain analysis increase sensitivity in detecting subclinical cardiac involvement in cardiomyopathies. Strain is frequently attenuated in cardiomyopathy and can be utilized for the evaluation of disease progression and the effect of therapeutic interventions.
In hypertrophic cardiomyopathy, typically, longitudinal function is reduced, while circumferential and radial function is elevated (Figure 1). The specific pattern of reduced and delayed longitudinal shortening and paradoxical systolic lengthening has been proposed as being specific for hypertrophic cardiomyopathy. Regional heterogeneity, typically with basal or mid septal longitudinal strain being most affected, appears to be distinctive to hypertrophic cardiomyopathy. Similar changes are not typically seen in ventricular hypertrophy induced by longstanding hypertension. Diastolic dysfunction appears early in hypertrophic cardiomyopathy.
Dilated cardiomyopathy is usually associated with reduced strain in all directions (Figure 2) and reduced left ventricular twist. In addition, left ventricular dyssynchrony is often seen in patients with dilated cardiomyopathy (see below). Nevertheless, the measurement of choice remains ejection fraction in this group of patients.
In restrictive cardiomyopathies attenuated longitudinal strain, but normal circumferential strain and left ventricular torsion are typical. Interestingly, ejection fraction may remain within normal limits until disease progression impairs circumferential strain. Constrictive pericarditis, conversely, is characterized by reduced circumferential strain and twist but preserved longitudinal function.
Figure 1: Left ventricular strain study in a patient with hypertrophic cardiomyopathy
Figure 2: Left ventricular radial strain study in a patient with dilated cardiomyopathy
Cancer therapy induced cardiomyopathy
Cancer patients receiving chemotherapy and/or radiation therapy may develop cardiomyopathy years or decades after ended theraphy. This new cohort of patients has arised due to the advances in detection and therapy of cancer and is becoming a major public health issue. As a consequence of improved survival, these patients will live long enough to develop cardiac complications of the cancer therapy.
Chemotherapy-treated patients with normal ejection fraction may have significantly reduced myocardial function assessed by speckle tracking strain echocardiography compared to healthy individuals. Left ventricular dysfunction may progress until overt congestive heart failure, therefore early detection and treatment of cardiotoxicity is crucial in order to reduce the development of clinical manifestations.
Heart transplant recipients and cardiac function
Heart transplantation is the gold standard therapy for selected patients with end-stage heart failure, with 1-year survival approaching 90%. Graft dysfunction is a major cause of morbidity and mortality in heart transplant recipients. Importantly, not all cases of early cardiac allograft dysfunction can be explained by rejection. Early left ventricular function in heart transplant recipients is determined by immune response, and a variety of non-immune factors such as ischemia-reperfusion injury, post-surgical sympathetic denervation, reduction of pre-heart transplant pulmonary hypertension and left ventricular preload, advanced age, post-transplantation infections, and donor variables including age, ischemic time and left ventricular hypertrophy. The search for non-invasive techniques to assess cardiac allograft function is a high priority objective for heart transplant professionals. Sensitive assessment of myocardial function by speckle tracking strain in heart transplant recipients with normal left ventricular function by traditional echocardiographic measures is a non-invasive screening tool in the identification of patients with poor clinical prognosis.
Speckle tracking and left ventricular dyssynchrony
Strain assessment has contributed to improved understanding of left ventricular dyssynchrony. However, current guidelines still define the indications for cardiac resynchronization therapy exclusively on the basis of clinical findings (heart failure symptoms, New York Heart Association class II-IV), left ventricular function (ejection fraction ≤ 35%), and electrocardiographic findings (QRS ≥ 120msec). Nevertheless, only about 70% of patients treated with cardiac resynchronization therapy respond to this treatment with improvement in left ventricular function. This reflects the clinical need for better patient selection and methods of therapy optimization.
Intraventricular dyssynchrony is commonly seen in patients with heart failure, and is believed to indicate more severe myocardial disease and poorer prognosis. One method to measure dyssynchrony is by assessing delay between anteroseptal radial strain and posterior (or inferior lateral) radial strain by speckle tracking echocardiography (Figure 3). Over 130 msec difference in time to peak radial strain between these two basal segments predicts response to cardiac resynchronization therapy. The standard deviation of time to peak longitudinal strains from 12 basal and mid segments may also be used to assess dyssynchrony. Values over 60 msec predict response to cardiac resynchronization therapy. Importantly, by combining radial and longitudinal dyssynchrony parameters a much higher accuracy is reached in predicting the response to cardiac resynchronization therapy.
Nevertheless, in spite of a significant number of various methods and dyssynchrony indices, there is still a lack of agreement on which indices should be utilized to predict cardiac resynchronization therapy response.
Figure 3: Left ventricular radial strain study in a patient with dyssynchrony
Speckle tracking in the detection of malignant arrhythmias
Patients with genetically diagnosed cardiomyopathy and relatives of patients with known heritable cardiac disease maybe mutation carriers without obvious myocardial dysfunction. These patients may eventually develop malignant arrhythmias even before myocardial changes can be shown with traditional imaging techniques. Accurate assessment of myocardial function is therefore particularly important in these patients. A recently introduced application of deformation imaging that quantifies temporal nonuniformity of maximum myocardial contraction is mechanical dispersion (Figure 4). This variable is a promising marker of risk for ventricular arrhythmias and sudden death. Mechanical dispersion can be assessed by either myocardial velocities or strain imaging and is calculated as the standard deviation of the time from onset R in the ECG to maximum myocardial shortening in 16 left and 6 right ventricular segments (Figure 4). Increased right ventricular mechanical dispersion above 29 msec is associated with increased risk for malignant arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy (Figure 5). Increased left ventricular mechanical dispersion is associated with malignant arrhythmias in long QT syndrome, dilated cardiomyopathy and in patients after myocardial infarctions.
Figure 4: Definition of contraction duration and mechanical dispersion in the right ventricle
Figure 5: Evolution of mechanical dispersion in arrhythmogenic right ventricular
Speckle tracking in ischemic heart disease
Changes in strain facilitate recognition of ischemic myocardium at rest and during stress echocardiography and may provide prognostic information. It may also help defining the transmural extent of myocardial infarction and the presence of viable myocardium. The ischemic myocardium is characterized by reduced or lacking regional systolic longitudinal (Figure 6) and circumferential shortening and radial thickening (Figure 7). Post systolic shortening after aortic valve closure is also a common finding in acute ischemia.
In patients with coronary artery disease infarct size might be assessed and the presence of coronary artery occlusions might be identified with speckle tracking echocardiography.   The size of the myocardial infarction may give important prognostic information while the detection of coronary artery occlusions may have important clinical implications in patients with non ST-elevation acute coronary syndrome. Although, coronary artery occlusion is found in about 25% of patients with non-ST elevation acute coronary syndrome, ECG has limited sensitivity to detect the presence of occlusion. Even though these patients may develop extensive myocardial damage, criteria for acute reperfusion therapy may not be fulfilled. Correct identification of coronary occlusion in non ST-elevation acute coronary syndrome may prevent irreversible myocardial damage in these patients by urgent reperfusion therapy as practiced in patients with ST-elevation myocardial infarctions. The direct observation of a developing systolic dysfunction combined with a post systolic shortening indicates acute myocardial ischemia .
The place of strain echocardiography in the detection and assessment of fibrosis and myocardial viability is not yet settled. Currently, combination of strain with low- dose dobutamine stress pertains the strongest evidence for the evaluation of myocardial viability.
Finally, increased mechanical dispersion (described above) assessed by strain echocardiography has been associated with increased risk of arrhythmic events, independently of left ventricular function assessed by ejection fraction in patients with ischemic heart disease. Since the majority of patients with ischemic heart disease and malignant arrhythmias have ejection fractions above 35%, there is a need for novel methods to identify risk in these patients.
Figure 6: Left ventricular longitudinal strain study of a patient with coronary artery occlusion
Figure 7: Left ventricular radial strain study of a patient with coronary artery occlusion
Clinical applications of 3D speckle tracking
Three dimensional (3D) speckle tracking echocardiography is a novel and promising commercially available tool to characterize and quantify myocardial segmental (Figure 8) and rotational mechanics (Figure 9). One possible application of the method is in the assessment of ventricular dyssyncrony. Assessment is done by measuring mechanical activation times derived from time-to-peak systolic strain of different segments, with the expectation that identification of the segments of latest mechanical activation could identify dyssynchrony and guide successful lead placement leading to optimal cardiac resynchronization therapy response.  However, there are only a few studies published so far using 3D speckle tracking in the clinical practice.
Figure 8: 3D speckle tracking area strain study in a healthy individual
Figure 9: 3D speckle tracking myocardial rotation study in a healthy individual
Right ventricular function and speckle tracking echocardiography
Longitudinal shortening is the major contributor to overall right ventricular function with an equal contribution of the right ventricular free wall and the interventricular septum. Assessment of right ventricular function by conventional 2D echocardiography is, however, challenging due to the complex right ventricular geometry and the strongly trabeculated inner wall contour. Speckle tracking echocardiography is promising tool in assessing regional and global right ventricular deformation in different directions in terms of both amplitude and timing, with the advantage of being less affected than tissue Doppler imaging by overall heart motion (Figure 10). In healthy individuals, peak systolic longitudinal strain in the free right ventricular wall is approximately -28 ± 4%. In diseases with right ventricular involvement, longitudinal deformation decrease and the base-to-apex gradient tends to disappear. Arrhythmogenic right ventricular cardiomyopathy has typical involvement of the right ventricular free wall with early reduction of longitudinal deformation and increased mechanical dispersion (Figure 11) . These changes can be readily assessed by speckle tracking echocardiography. Furthermore, strain abnormalities of the right ventricle can also be detected in pulmonary hypertension, as well as in amyloidosis and congenital heart diseases . In general, strain measurement is useful as an early indicator of right ventricular dysfunction.
Figure 10: Right ventricular strain study in a healthy individual
Figure 11: Right ventricular strain study in a patient with arrhythmogenic right ventricular cardiomyopathy