Editor's Note: This article is Part Two of a two-part Expert Analysis. Click here for Part One.

Strain is an advanced echocardiographic technique that assesses myocardial function by evaluating deformation of the myocardium. It is reported as a dimensionless percentage of myocardial deformation and may be determined using tissue Doppler imaging or speckle-tracking echocardiography. Tissue Doppler imaging, an earlier technique, was limited by angle dependency and labor-intensive acquisition. Conversely, speckle-tracking echocardiography is less angle-dependent but comes with its own imaging limitations, including dependency on two-dimensional (2D) image quality, vendor software "normal value" variability, and loading condition variability, and requires training and expertise.

Although attempts were made to standardize terminology for deformation imaging,^1,2 differing normal values for varying vendor software remain. A study compared global longitudinal strain (GLS) obtained from nine different vendors and although the reproducibility of the GLS measurements were similar to other echocardiographic parameters (including left ventricular [LV] ejection fraction), there was a small but significant difference in strain measurements among vendors.³

Inter-vendor-related software differences remain a challenge for strain imaging. Certain software performs spatial and temporal smoothing based on normal deformation models, which may compromise the accuracy of the results.¹ A study compared the strain values obtained using vendor-specific software to values obtained via vendor-independent software and found that there was agreement among the longitudinal strain but disagreement with radial and circumferential strain.⁴ On a larger scale, a meta-analysis evaluated normal values for LV GLS in 24 studies and found that normal values ranged from -15.9 to -22.1%. An even larger spread for normal global radial strain was present (35.1-59%).⁵ Compounded upon the variability of normal values obtained with strain imaging, there are also conflicting data on whether age, gender, and race affect strain values. Some studies report variation in strain values with age⁶ and gender⁷ where others found no change.⁸ Strain values are sensitive to preload and afterload,⁹ and one could also hypothesize that heart rate might influence normal values.

Longitudinal follow-up is challenging when different software with different normal values are utilized, and it is unclear how to interpret the serial strain data performed on different software. In addition, if strain imaging is performed on the same device but a software upgrade has occurred in the interim, differences may exist. Also, due to variations in age-specific values at present, when examining strain parameters in the same patient who has aged over the time period of observation, it is unclear if the difference represents "normal" aging or a true pathologic change.

Multiple possible reasons lead to the variability of differing inter-vendor strain values, including image quality and acquisition, post-processing of data, and patient loading conditions. Speckle-tracking echocardiography may be suboptimal in patients with poorly defined subendocardial borders and in images with near-field ("bang") or sidelobe artifacts. Due to poor endocardial visualization and previously mentioned artifacts, automatic software packages that trace the endocardium may be subject to error. Verification of appropriate tracking of automated tracings must be performed, and this may be time consuming for daily clinical practice.

Strain patterns have been described in certain cardiomyopathies including hypertrophic cardiomyopathy and with cardiac amyloid disease.^10,11 A small study compared 55 patients with cardiac amyloid to controls with LV hypertrophy (from either aortic stenosis [AS] or hypertrophic cardiomyopathy) and noticed a reduction of basal GLS compared with the ventricular apex in patients with cardiac amyloidosis.¹² Although this "bulls-eye" pattern was seen in this small cohort with cardiac amyloidosis, it is not clear if this pattern is present in all patients with cardiac amyloid. Also, the true sensitivity and specificity of this pattern in the general cardiac amyloid population is unknown. It is also unknown if differences exist in the various subtypes of amyloid. Reduction in basal GLS is not specific to cardiac amyloid and can be seen with other myopathic processes such as basal hypertrophy cardiomyopathy (HCM).

In patients with HCM, there are varying phenotypic presentations of the disease. The use of cardiac magnetic resonance (CMR) in these patients is clinically useful, and CMR is utilized for its ability to assess not only LV wall thickness and function but also myocardial fibrosis.¹³ Strain imaging may assess LV function, but it does not provide the other clinically useful information that can be obtained from CMR. Regional myocardial strain can be challenging because normal values may differ by region. Also, to date, regional strain values found are of limited clinical utility because there have been no large trials published that evaluate the clinical implications of low regional strain values in patients with HCM.

More recently, groups are investigating the use of strain imaging to identify early LV dysfunction in patients with AS as noted by reduced strain. A small study found that there was improvement in strain values after aortic valve replacement in patients with severe AS; however, the prognostic implications of these changes are not known.¹⁴ It has yet to be shown how much absolute reduction in strain is significant in this population. The most recent valvular heart disease guidelines state that further studies regarding strain in assessment for AS severity are needed before consideration of clinical usefulness.¹⁵ Reduction in strain due to acquisition error or varying software may be misleading, and it is not recommended that patients be referred for surgical intervention based strictly on this finding. Also, subclinical or even known coronary disease can be found in this population. The presence of coronary disease may affect strain values; the combination of AS with coronary disease and the effect on strain values has also not been studied in a large population of this mixed disease.

The various forms of strain—longitudinal, radial and circumferential—are reported as simple numerical values. A further concern about implementation of strain in routine clinical echocardiographic exams is that once these numerical parameters are automatically generated, there is a risk that clinicians will rely solely on these values and fail to exam the nuances of the images, which may provide more or different information. We have already witnessed how some rely solely on Doppler parameters to report grades of LV diastolic dysfunction without taking into consideration the patient's presenting symptoms, exam findings, or other important clinical information. In a similar way, the routine implementation of strain could cause a wave of diagnoses of "subclinical" myocardial dysfunction without knowledge of whether this condition truly exists for that particular patient. This may be especially problematic in oncology patients for whom life-saving chemotherapy might be held or modified due to a decreased strain value, yet the ultimate change in LV function could be small enough to be tolerated in the face of a potentially curative treatment. This issue highlights the difference between statistically significant change and clinically significant change. Also, the exact change in strain value needed to predict a significant change in this population of patients remains unclear and subject to inter-reader measurement variability.

Strain imaging can be used to evaluate deformation of the myocardium and, at present, is best utilized as a research tool with limited everyday clinical application. Further studies are needed to standardize normal values and to determine if there are age, gender, and race variabilities. Care should be taken when recognizing specific strain patterns (such as that attributed to cardiac amyloid) in general populations because the true sensitivity and specificity in such a situation is unclear. The challenge could be that when routinely applied to all subjects, the accuracy of strain cut-off values and regional patterns may differ from those currently derived from specialized populations. The time and expertise required to accurately obtain strain values and the currently unknown disease-specific accuracy are impediments to routinely adding this new technology to a complete clinical 2D-transthoracic echocardiogram. Thus, strain should be used cautiously as an adjunctive modality along with other echocardiographic parameters to evaluate LV function.

References

1. Voigt JU, Pedrizzetti G, Lysyansky P, et al. Definitions for a common standard for 2D speckle tracking echocardiography: consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging. Eur Heart J Cardiovasc Imaging 2015;16:1-11.
2. Thomas JD, Badano LP. EACVI-ASE-industry initiative to standardize deformation imaging: a brief update from the co-chairs. Eur Heart J Cardiovasc Imaging 2013;14:1039-40.
3. Farsalinos KE, Daraban AM, Ünlü S, Thomas JD, Badano LP, Voigt JU. Head-to-Head Comparison of Global Longitudinal Strain Measurements among Nine Different Vendors The EACVI/ASE Inter-Vendor Comparison Study. J Am Soc Echocardiogr 2015;28:1172-81,e2.
4. Risum N, Ali S, Olsen NT, et al. Variability of global left ventricular deformation analysis using vendor dependent and independent two-dimensional speckle-tracking software in adults. J Am Soc Echocardiogr 2012;25:1195-203.
5. Yingchoncharoen T, Agarwal S, Popović ZB, Marwick TH. Normal ranges of left ventricular strain: a meta-analysis. J Am Soc Echocardiogr 2013;26;185-91.
6. Zghal F, Bougteb H, Réant P, Lafitte S, Roudaut R. Assessing global and regional left ventricular myocardial function in elderly patients using the bidimensional strain method. Echocardiography 2011;28:978-82.
7. Dalen H, Thorstensen A, Aase SA, et al. Segmental and global longitudinal strain and strain rate based on echocardiography of 1266 healthy individuals: the HUNT study in Norway. Eur J Echocardiogr 2010;11:176-83.
8. Fernandes VR, Edvardsen T, Rosen BD, et al. The influence of left ventricular size and global function on regional myocardial contraction and relaxation in an adult population free of cardiovascular disease: a tagged CMR study of the MESA cohort. J Cardiovasc Magn Reson 2007;9:921-30.
9. Burns AT, La Gerche A, D'hooge J, MacIsaac AI, Prior DL. Left ventricular strain and strain rate: characterization of the effect of load in human subjects. Eur J Echocardiogr 2010;11:283-9.
10. Koyama J, Ray-Sequin PA, Falk RH. Longitudinal myocardial function assessed by tissue velocity, strain, and strain rate tissue Doppler echocardiography in patients with AL (primary) cardiac amyloidosis. Circulation 2003;107:2446-52.
11. Serri K, Reant P, Lafitte M, et al. Global and regional myocardial function quantification by two-dimensional strain: application in hypertrophic cardiomyopathy. J Am Coll Cardiol 2006;47:1175-81.
12. Phelan D, Collier P, Thavendiranathan P, et al. Relative apical sparing of longitudinal strain using two-dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis. Heart 2012;98:1442-8.
13. To AC, Dhillon A, Desai MY. Cardiac magnetic resonance in hypertrophic cardiomyopathy. JACC Cardiovasc Imaging 2011;4:1123-37.
14. Delgado V, Tops LF, van Bommel RJ, et al. Strain analysis in patients with severe aortic stenosis and preserved left ventricular ejection fraction undergoing surgical valve replacement. Eur Heart J 2009;30:3037-47.
15. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:e57-e185.

Keywords: Amyloidosis, Anthracyclines, Aortic Valve, Aortic Valve Stenosis, Arrhythmias, Cardiac, Benzimidazoles, Cardiomyopathies, Cardiomyopathy, Dilated, Cardiomyopathy, Hypertrophic, Cardiotoxicity, Coronary Disease, Echocardiography, Endocardium, Heart Atria, Heart Failure, Heart Rate, Heart Ventricles, Hypertrophy, Magnetic Resonance Spectroscopy, Mitral Valve, Mitral Valve Insufficiency, Myocardium, Tetrazoles, Ventricular Dysfunction, Diagnostic Imaging

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