Echocardiographic Strain Has Clinical Use
Editor's Note: This article is Part One of a two-part Expert Analysis. Click here for Part Two.
Strain imaging by speckle tracking is a relative newcomer in the world of echocardiography, with the technique described in 20041 and clinical applications appearing around 2005.2 In the short interim, it has demonstrated its value in a wide array of clinical situations. For this discussion, we will focus on the left ventricle (LV) and associated abnormalities, though there is also promising research on the left atrium and right heart, which have traditionally been hard to characterize.
Much concern has been raised in the past over the vendor variability in strain calculations, with more than 50% variation noted in some studies, previously requiring the same hardware and software for reliable follow-up.3 This has largely been mitigated by the American Society of Echocardiography and the European Association of Cardiovascular Imaging that convened a strain standardization task force in collaboration with industry to address this4 using computer simulations5 and clinical studies,6 which showed now that vendor differences have narrowed to 1-2% (absolute) lower than structural measurements (like posterior wall thickness) and with better interobserver variability than the ejection fraction (EF).
LVEF is helpful for predicting outcomes in many cardiac conditions7 but has important limitations due both to technical reasons and the complex relationship in preload and afterload.8,9 Kalam et al. looked at a variety of trials involving diverse pathologies, which consistently showed that reduced global longitudinal strain (GLS) was associated with adverse outcomes including mortality, much like that of LVEF.10
One key field where strain has been widely adopted is oncology. Anthracyclines cause a known, predictable, dose-dependent cardiomyopathy.11 Heart failure (HF) in the setting of anthracycline usage has a significantly higher mortality rate than idiopathic dilated cardiomyopathy (2-year mortality up to 60%, adjusted hazard ratio 3.5 compared with idiopathic cardiomyopathy).12 Sawaya et al. showed that unlike LVEF, reduced GLS <-19% at completion of chemotherapy predicted future LV dysfunction.13 Additionally, a relative decrease in GLS of 10-15% is predictive of future cardiotoxicity.13,14 In patients receiving trastuzumab, a relative reduction in GLS of over 11% (95% confidence interval 8-15%) was highly predictive of reductions in LVEF.14 Ali et al. have also demonstrated increased rates of symptomatic HF and cardiac death in those found to have normal LVEF but impaired GLS (<-17.5%) prior to initiation of anthracyclines.15
Studies are now ongoing for prophylactic therapy in those at risk of chemotherapy-induced HF. The randomized multi-arm PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial did not see EF preservation with metoprolol but did with candesartan.16 GLS was not significantly different in either treatment arm. Further randomized control trials17,18 may help us guide cardioprotective therapy.
Echocardiography plays a vital role in the screening, diagnosis, and management of hypertrophic cardiomyopathy (HCM).19 Hypertrophy and fibrosis progress despite a preservation in EF.20 A reduction in strain is associated with fibrosis,21 increased risk for ventricular arrhythmias,22 HF, and death.23 Differentiating maladaptive hypertrophy from that of physiologic adaptation ("athlete's heart") or other causes of hypertrophy is challenging. Afonso et al. compared HCM, hypertensive heart, and athlete's heart patients and found that GLS was reduced in HCM patients compared with the other hypertrophic patients.24 Additionally, when compared with hypertensive heart disease, HCM had a significantly decreased strain.25
In patients with amyloid light-chain (AL), cardiac involvement is associated with significantly reduced survival time.26 Cardiac infiltration leads to LV hypertrophy, which can be confused with LV hypertrophy or HCM and delay diagnosis. In cardiac amyloid, LVEF is often not affected early, and diastolic e´ velocities are minimally altered until late in the disease process.27 Reduction in longitudinal strain with relative sparing at the apex is highly predictive of cardiac amyloid compared with other hypertrophic patients.28 If average strain in the apex is twice the average of the remainder of cardiac segments on a strain polar map ("bulls eye"), amyloid is highly likely. Routine use can differentiate apical sparing from other causes of LV hypertrophy, such as HCM, which exhibits isolated septal impairment or aortic stenosis (AS), which is patchy.28,29
One of the most important recommendations from the recent valvular heart disease guidelines is the importance of intervening prior to the development of overt ventricular dysfunction,30 emphasizing the importance of looking beyond EF. For example, in patients with AS, reduced GLS was an independent predictor for death and major cardiac events in those with severe symptomatic31,32 and asymptomatic33 AS.
In regurgitant valvular disease, depression in EF is a late change and can lead to irreversible reduction in systolic function. In patients with severe mitral regurgitation, a reduction in strain pre-operatively can be predictive of depressed LVEF post-operatively.34-36 More importantly, Witkowski et al. followed patients after mitral valve repair and found GLS <-19.9 % to be independently predictive of long-term reduction in systolic function.37 Alaishi et al. have also seen similar trends after mitral valve surgery, with abnormalities in GLS being associated with post-operative EF reductions and increased mortality.38
In summary, strain imaging by echocardiography has been shown to add unique data that can guide diagnosis and management in a host of clinical situations that are commonly encountered. Because of this utility, strain should be used as an increasingly routine portion of the standard echocardiographic exam.
- Leitman M, Lysyansky P, Sidenko S, et al. Two-dimensional strain-a novel software for real-time quantitative echocardiographic assessment of myocardial function. J Am Soc Echocardiogr 2004;17:1021-9.
- Notomi Y, Lysyansky P, Setser RM, et al. Measurement of ventricular torsion by two-dimensional ultrasound speckle tracking imaging. J Am Coll Cardiol 2005;45:2034-41.
- Takigiku K, Takeuchi M, Izumi C, et al. Normal range of left ventricular 2-dimensional strain: Japanese Ultrasound Speckle Tracking of the Left Ventricle (JUSTICE) study. Circ J 2012;76:2623-32.
- 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. J Am Soc Echocardiogr 2015;28:183-93.
- D'hooge J, Barbosa D, Gao H, et al. Two-dimensional speckle tracking echocardiography: standardization efforts based on synthetic ultrasound data. Eur Heart J Cardiovasc Imaging 2016;17:693-701.
- 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;28:1171-81, e2.
- Solomon SD, Anavekar N, Skali H, et al. Influence of ejection fraction on cardiovascular outcomes in a broad spectrum of heart failure patients. Circulation 2005;112:3738-44.
- Sagawa K. The end-systolic pressure-volume relation of the ventricle: definition, modifications and clinical use. Circulation 1981;63:1223-7.
- Otterstad JE. Measuring left ventricular volume and ejection fraction with the biplane Simpson's method. Heart 2002;88:559-60.
- Kalam K, Otahal P, Marwick TH. Prognostic implications of global LV dysfunction: a systematic review and meta-analysis of global longitudinal strain and ejection fraction. Heart 2014;100:1673-80.
- Neilan TG, Jassal DS, Perez-Sanz TM, et al. Tissue Doppler imaging predicts left ventricular dysfunction and mortality in a murine model of cardiac injury. Eur Heart J 2006;27:1868-75.
- Felker GM, Thompson RE, Hare JM, et al. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med 2000;342:1077-84.
- Sawaya H, Sebag IA, Plana JC, et al. Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab. Circ Cardiovasc Imaging 2012;5:596-603.
- Negishi K, Negishi T, Hare JL, Haluska BA, Plana JC, Marwick TH. Independent and incremental value of deformation indices for prediction of trastuzumab-induced cardiotoxicity. J Am Soc Echocardiogr 2013;26:493-8.
- Ali MT, Yucel E, Bouras S, et al. Myocardial Strain Is Associated with Adverse Clinical Cardiac Events in Patients Treated with Anthracyclines. J Am Soc Echocardiogr 2016;29:522-27.e3.
- Gulati G, Heck SL, Ree AH, et al. Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 x 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. Eur Heart J 2016;37:1671-80.
- Yu A. Carvedilol for the Prevention of Anthracycline/Anti-HER2 Therapy Associated Cardiotoxicity Among Women With HER2-Positive Breast Cancer Using Myocardial Strain Imaging for Early Risk Stratification (ClinicalTrials.gov website). 2014. Available at: https://clinicaltrials.gov/ct2/show/NCT02177175. Accessed 12/12/2016.
- Pituskin E, Haykowsky M, Mackey JR, et al. Rationale and design of the Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research Trial (MANTICORE 101--Breast): a randomized, placebo-controlled trial to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer using cardiac MRI. BMC Cancer 2011;11:318.
- Williams LK, Gruner CH, Rakowski H. The role of echocardiography in hypertrophic cardiomyopathy. Curr Cardiol Rep 2015;17:6.
- Urbano-Moral JA, Rowin EJ, Maron MS, Crean A, Pandian NG. Investigation of global and regional myocardial mechanics with 3-dimensional speckle tracking echocardiography and relations to hypertrophy and fibrosis in hypertrophic cardiomyopathy. Circ Cardiovasc Imaging 2014;7:11-9.
- Popović ZB, Kwon DH, Mishra M, et al. Association between regional ventricular function and myocardial fibrosis in hypertrophic cardiomyopathy assessed by speckle tracking echocardiography and delayed hyperenhancement magnetic resonance imaging. J Am Soc Echocardiogr 2008;21:1299-305.
- Haland TF, Almaas VM, Hasselberg NE, et al. Strain echocardiography is related to fibrosis and ventricular arrhythmias in hypertrophic cardiomyopathy. Eur Heart J Cardiovasc Imaging 2016;17:613-21.
- Hartlage GR, Kim JH, Strickland PT, et al. The prognostic value of standardized reference values for speckle-tracking global longitudinal strain in hypertrophic cardiomyopathy. Int J Cardiovasc Imaging 2015;31:557-65.
- Afonso L, Kondur A, Simegn M et al. Two-dimensional strain profiles in patients with physiological and pathological hypertrophy and preserved left ventricular systolic function: a comparative analyses. BMJ Open 2012;2: e001390.
- Kato TS, Noda A, Izawa H, et al. Discrimination of nonobstructive hypertrophic cardiomyopathy from hypertensive left ventricular hypertrophy on the basis of strain rate imaging by tissue Doppler ultrasonography. Circulation 2004;110:3808-14.
- Merlini G, Stone MJ. Dangerous small B-cell clones. Blood 2006;108:2520-30.
- Koyama J, Ray-Sequin PA, Davidoff R, Falk RH. Usefulness of pulsed tissue Doppler imaging for evaluating systolic and diastolic left ventricular function in patients with AL (primary) amyloidosis. Am J Cardiol 2002;89:1067-71.
- 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.
- Phelan D, Thavendiranathan P, Popovic Z, et al. Application of a parametric display of two-dimensional speckle-tracking longitudinal strain to improve the etiologic diagnosis of mild to moderate left ventricular hypertrophy. J Am Soc Echocardiogr 2014;27:888-95.
- 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:e57-185.
- Dahl JS, Videbæk L, Poulsen MK, Rudbæk TR, Pellikka PA, Møller JE. Global strain in severe aortic valve stenosis: relation to clinical outcome after aortic valve replacement. Circ Cardiovasc Imaging 2012;5:613-20.
- Nagata Y, Takeuchi M, Wu VC, et al. Prognostic value of LV deformation parameters using 2D and 3D speckle-tracking echocardiography in asymptomatic patients with severe aortic stenosis and preserved LV ejection fraction. JACC Cardiovasc Imaging 2015;8:235-45.
- Yingchoncharoen T, Gibby C, Rodriguez LL, Grimm RA, Marwick TH. Association of myocardial deformation with outcome in asymptomatic aortic stenosis with normal ejection fraction. Circ Cardiovasc Imaging 2012;5:719-25.
- de Isla LP, de Agustin A, Rodrigo JL, et al. Chronic mitral regurgitation: a pilot study to assess preoperative left ventricular contractile function using speckle-tracking echocardiography. J Am Soc Echocardiogr 2009;22:831-8.
- Cho EJ, Park SJ, Yun HR, et al. Predicting Left Ventricular Dysfunction after Surgery in Patients with Chronic Mitral Regurgitation: Assessment of Myocardial Deformation by 2-Dimensional Multilayer Speckle Tracking Echocardiography. Korean Circ J 2016;46:213-21.
- Pandis D, Sengupta PP, Castillo JG, et al. Assessment of longitudinal myocardial mechanics in patients with degenerative mitral valve regurgitation predicts postoperative worsening of left ventricular systolic function. J Am Soc Echocardiogr 2014;27:627-38.
- Witkowski TG, Thomas JD, Debonnaire PJ, et al. Global longitudinal strain predicts left ventricular dysfunction after mitral valve repair. Eur Heart J Cardiovasc Imaging 2013;14:69-76.
- Alashi A, Mentias A, Patel K et al. Synergistic Utility of Brain Natriuretic Peptide and Left Ventricular Global Longitudinal Strain in Asymptomatic Patients With Significant Primary Mitral Regurgitation and Preserved Systolic Function Undergoing Mitral Valve Surgery. Circ Cardiovasc Imaging 2016;9: e004451.
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