Medical imaging has never been static. With each new technological advance, we view our patients in a different way. Sometimes it is dramatically different from the outset, and sometimes the differences are subtler. As new ways of depicting how our bodies appear or function emerge, older methods may be considered redundant or obsolete and become relegated to treatises of historical methods. With each step forward, we encounter at least two fundamental dilemmas: the first is how and when to apply a new clinical tool, and the second is if we need to rethink some of our older established ideas as we integrate and assimilate new technologies and come to appreciate the usefulness and limitations of new tools.

Cardiac imaging, and especially cardiac ultrasound, is no exception to this basic principle. As M-mode imaging evolved, we could see how structures moved closer to or farther away from our transducer; we could estimate chamber dimensions, which allowed us to make the first truly meaningful ultrasonic estimations of ejection fraction. These M-mode images were often used together with carotid pulse contours, apex cardiograms, and phonocardiograms to better appreciate the timing of events on what today seems like primitive instrumentation. As phased array technology developed, we could visualize a more integrated view of cardiac chambers; two-dimensional (2D) echocardiography evolved to be a modality that was broadly used for the early detection of cancer treatment-related cardiac dysfunction.¹ In the early 1980s, Doppler imaging allowed us to look at speed and direction of blood flow. Many questioned what use this could possibly have. If 2D ultrasound provided good images, wasn't it obvious that blood flowed through these chambers? It took time to appreciate the true value of Doppler flow patterns, but the techniques have become embedded in our ultrasound examinations and are considered essential components of cardiac imaging. Three-dimensional (3D) imaging provides us with an even better appreciation of cardiac structure. Each facet of this evolution did not take place in a vacuum but rather required us to rethink what we knew before and prepare for new insights that might raise questions as we approach ultrasound with the broader views initiated through technological progress.

At each stage, there were those who questioned how much of what we were doing added real value to how we assess our patients. How much time were we investing to show what we already knew in ways that added only modest incremental information? Was the incremental time and resources expended a reasonable and cost-effective way to add value? And, of especial relevance for the patient with cancer, did it help with the age-old question of the balance of risk and benefit; the benefit of oncologic efficacy versus a risk of cardiac dysfunction.²

We have now encountered yet another novel cardiac imaging parameter. Technology has evolved to the point where areas of the heart can be observed at markedly increased frame rates, an evolution that allows us to measure segmental deformation. These techniques now are commonly referred to as strain imaging. Strain is the normalized, dimensionless measure of deformation of a segment of myocardium in response to an applied force or stress. In cardiac imaging, we can now measure the rate of deformation of the ventricular wall in various dimensions, providing a new facet in our endeavor to appreciate early myocardial dysfunction. Strain imaging, although not yet fully integrated, may become especially relevant as we appreciate and attempt to characterize diastolic function more accurately. Heretofore, we have lacked insight regarding parameters of diastolic change from a prognostic standpoint and as we consider interventions to manage diastolic function-related diseases. These evolving applications are being explored; we eagerly await insight as to how we can better appreciate early and subclinical alterations in how the hearts of patients with cancer function and respond to the stresses of their disease and its treatment.

With any new technique, three basic questions must be addressed:

1. In whom should we be using it?
2. How should the newly derived data be integrated into what we already know?
3. Once sufficiently developed and integrated into our standard testing, how, and to what extent, must established ideas and practice patterns evolve as the new technique is integrated?

To address these questions, we first must ask what strain imaging adds. The basic answer is that it enhances sensitivity of the cardiac ultrasound examination. There is no greater evidence for this than what we have learned in the evaluation of patients with coronary artery disease (CAD) over the last decade. Strain measurements in patients with CAD could be expected to identify severe coronary stenosis with good sensitivity and fair specificity even in the absence of segmental wall motion abnormalities.³ The technique has also shown promise in serving to enhance our clinical confidence in one of the most difficult and stressful of conditions for the clinician: the evaluation of those presenting in emergency centers for acute chest pain evaluation. Interestingly, a recent study showed that myocardial deformation imaging could identify at-risk patients with suspected acute coronary syndrome without specific electrocardiographic changes or myocardial enzyme abnormalities.⁴ Furthermore, strain imaging can help identify higher-risk patients after coronary interventions.^5,6 Clearly, the technology has the ability to augment what the skilled but naked eye of the reader cannot otherwise visualize.

But do these benefits translate sufficiently to the patient with cancer whose cardiac dysfunction differs from those with regional wall motion abnormalities? Much suggests that it does. Recent papers note that in evaluating patients receiving anthracycline therapy, longitudinal peak systolic strain might be a more accurate way for assessing myocardial function because it detects a specific segmental dysfunction pattern in these patients; there is good correlation between strain-based dysfunction and a significant drop in left ventricular ejection fraction.⁷ Additionally, Santoro et al. noted that in anthracycline-treated patients, both 2D and 3D strain methods have the potential to detect subclinical changes in patients receiving cardiotoxic drugs better than ejection fraction-based evaluations.⁸ Others have also contributed to our expanding knowledge regarding this evolving modality.^9-12 Strain imaging allows us to identify dysfunction earlier and, together with our oncology colleagues, balance risk and benefit with new insight and authority. During our patients' cancer treatments, we are now able to consider substituting less-toxic regimens or cardioprotective administration schedules. In the post-treatment survivorship period, we can better optimize the timing of cardiac-sparing interventions (i.e., the introduction of specific heart failure medications). Proving the ultimate benefit of this technology will, of course, be challenging because of the multitude of factors that play confounding roles in the management of patients with cancer because anti-cancer modalities are not the only causes of impaired cardiac function in this population. Nevertheless, data that are available now strongly suggest that early recognition of cardiac dysfunction is important and should be considered as we evaluate those receiving cardiotoxic regimens.

Additionally, the currently available systems that allow for strain imaging can produce patterns that are easy to visualize as "polar maps" (mostly longitudinal deformation) that illustrate spatial patterns that enhance our differential diagnosis. Such is the case for certain types of cardiomyopathic processes such as infiltrative disease and stress induced cardiomyopathy; these entities may be quite subtle when the clinician is looking at a collection of 2D images in the abstract.^13,14 But beyond this, the deformation measures themselves have demonstrated prognostic value in those settings.¹⁵ Strain imaging, in particular the global longitudinal value, has recently shown all-cause mortality prognostic value in a study looking into patients with heart failure with reduced ejection fraction, when comparing against all other traditional echocardiographic parameters.¹⁶ However, perhaps no other potential use or application has garnered more interest or enthusiasm than for prediction of dysfunction in patients undergoing potentially cardiotoxic anti-cancer therapies. Several reports have indicated promising results in the recognition of subclinical dysfunction, particularly in (but not limited to) the population of patients with breast cancer, which unfortunately continues to be a large-scale health problem in the United States.^10,11,17

Significant progress has been achieved with the use of this technology, but in terms of user confidence regarding uniformity and its ability to provide meaningful, consistent results, strain has not yet been fully accepted into the clinician's armamentarium. Basic challenges, including image quality, persist, as do variances between the different devices that are currently available. To move us farther, a joint standardization task force between professional societies and industry was initiated in 2010 to reduce inter-vendor variability of strain measures, and these efforts have produced some initial results.^18-20

In our daily practice, we see many patients with small changes in ejection fraction, and strain may help us identify those who need more careful scrutiny. We recognize that 2D ultrasound is imperfect as we follow our patients; however, the margins of error in estimating ejection fraction, while less troubling than in the past, continue to generate clinical uncertainty. Strain gives us further insight. As we acquire more experience, we anticipate that the importance of this technique will expand.

Certainly, further research with consistent results is welcomed and anticipated. New information is being published monthly with incremental results on the use of this technology, and we are likely to have substantial added knowledge in the very near future. As with any new technology, clinical acceptance will be gradual. But just as with Doppler and 3D imaging before it, strain imaging will further evolve over time. For many of us treating and managing patients with cancer on a daily basis, it is time for strain to join the mainstream of noninvasive cardiac techniques and assist us in the management of our clinically challenging patients to whom we must provide the most advanced and sophisticated methods to assist them in their battles against cancer.

References

1. Ewer MS, Ali MK, Mackay B, et al. A comparison of cardiac biopsy grades and ejection fraction estimations in patients receiving Adriamycin. J Clin Oncol 1984;2:112-7.
2. Ewer MS, Ewer SM. Trastuzumab cardiotoxicity: the age-old balance of risk and benefit. Br J Cancer 2016;115:1441-2.
3. Li L, Zhang PY, Ran H, Dong J, Fang LL, Ding QS. Evaluation of left ventricular myocardial mechanics by three-dimensional speckle tracking echocardiography in the patients with different graded coronary artery stenosis. Int J Cardiovasc Imaging 2017;Apr 28:[Epub ahead of print].
4. Schroeder J, Hamada S, Gründlinger N, et. al. Myocardial deformation by strain echocardiography identifies patients with acute coronary syndrome and non-diagnostic ECG presenting in a chest pain unit: a prospective study of diagnostic accuracy. Clin Res Cardiol 2016;105:248-56.
5. Lacalzada J, de la Rosa A, Izquierdo MM, et.al. Left ventricular global longitudinal systolic strain predicts adverse remodeling and subsequent cardiac events in patients with acute myocardial infarction treated with primary percutaneous coronary intervention. Int J Cardiovasc Imaging 2015;31:575-84.
6. Cong T, Sun Y, Shang Z, et.al. Prognostic Value of Speckle Tracking Echocardiography in Patients with ST-Elevation Myocardial Infarction Treated with Late Percutaneous Intervention. Echocardiography 2015;32:1384-91.
7. Toufan M, Pourafkari L, Ghahremani Nasab L, et al. Two-dimensional strain echocardiography for detection of cardiotoxicity in breast cancer patients undergoing chemotherapy. J Cardiovasc Thorac Res 2017;9:29-34.
8. Santoro C, Arpino G, Esposito R, et al. 2D and 3D strain for detection of subclinical anthracycline cardiotoxicity in breast cancer patients: a balance with feasibility. Eur Heart J Cardiovasc Imaging 2017;18:930-6.
9. Okuma H, Noto N, Tanikawa S, et al. Impact of persistent left ventricular regional wall motion abnormalities in childhood cancer survivors after anthracycline therapy: Assessment of global left ventricular myocardial performance by 3D speckle-tracking echocardiography. J Cardiol 2017;70:396-401.
10. Charbonnel C, Convers-Domart R, Rigaudeau S, et al. Assessment of global longitudinal strain at low-dose anthracycline-based chemotherapy, for the prediction of subsequent cardiotoxicity. Eur Heart J Cardiovasc Imaging 2017;18:392-401.
11. Tang Q, Jiang Y, Xu Y, Xia H. Speckle tracking echocardiography predicts early subclinical anthracycline cardiotoxicity in patients with breast cancer. J Clin Ultrasound 2017;45:222-30.
12. 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.
13. Sosa S, Banchs J. Early recognition of apical ballooning syndrome by global longitudinal strain using speckle tracking imaging--the evil eye pattern, a case series. Echocardiography 2015;32:1184-92.
14. 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.
15. Barros-Gomes S, Williams B, Nhola LF, et.al. Prognosis of Light Chain Amyloidosis With Preserved LVEF: Added Value of 2D Speckle-Tracking Echocardiography to the Current Prognostic Staging System. JACC Cardiovasc Imaging 2017;10:398-407.
16. Sengeløv M, Jørgensen PG, Jensen JS, et.al. Global Longitudinal Strain Is a Superior Predictor of All-Cause Mortality in Heart Failure With Reduced Ejection Fraction. JACC Cardiovasc Imaging 2015;8:1351-9.
17. Sawaya H, Sebag IA, Plana JC, et.al. Early detection and prediction of cardiotoxicity in chemotherapy-treated patients. Am J Cardiol 2011;107:1375-80.
18. Kaul S, Miller JG, Grayburn PA, et al. A suggested roadmap for cardiovascular ultrasound research for the future. J Am Soc Echocardiogr 2011;24:455-64.
19. 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.
20. Yang H, Marwick TH, Fukuda N, et al. Improvement in Strain Concordance between Two Major Vendors after the Strain Standardization Initiative. J Am Soc Echocardiogr 2015;28:642-8.e7.

Keywords: Cardiotoxicity, Stroke Volume, Coronary Artery Disease, Acute Coronary Syndrome, Diagnosis, Differential, Pharmaceutical Preparations, Early Detection of Cancer, Imaging, Three-Dimensional, Echocardiography, Diastole, Anthracyclines, Myocardium, Cardiomyopathies, Coronary Stenosis, Heart Failure, Chest Pain

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