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 trials^17,18 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 symptomatic^31,32 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.

References

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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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