40765507
40765507
                                                               ABSTRACT: Assessment of left ventricular systolic function is essential for diagnosing and managing cardiac diseases
                                                               and provides important prognostic information to the treating clinician. However, traditional methods for assessing left
                                                               ventricular systolic function such as ejection fraction are limited by their reliance on geometric assumptions, subjective
                                                               reader interpretation, sensitivity to loading conditions and volume, and reflection of a single plane of motion. In addition
                                                               to interobserver and intraobserver variability and technical confounders, this evaluation is complicated by the complex
                                                               3-dimensional organization of the myocardial fibers, which are oriented longitudinally in the subendocardium, transversely
                                                               in the midmyocardium, and obliquely in the subepicardium. Conversely, 2-dimensional speckle-tracking echocardiography
                                                               measures left ventricular deformation as myocardial strain in the 3 planes of chamber motion: longitudinal, circumferential,
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                                                               and radial. From a clinical perspective, left ventricular global longitudinal strain offers superior diagnostic and prognostic value
                                                               across the spectrum of cardiovascular disorders compared with ejection fraction, is highly reproducible, and detects subclinical
                                                               dysfunction before the ejection fraction declines. Given the expanding clinical utility of speckle-tracking echocardiography and
                                                               the incremental prognostic and therapeutic value of integrating global longitudinal strain into clinical practice as a potential
                                                               biomarker, the objectives of this scientific statement are (1) to review the principles and technical aspects of speckle-tracking
                                                               echocardiography strain imaging; (2) to provide a practical, evidence-based review of the application of speckle-tracking
                                                               echocardiography in heart failure, cardiomyopathies, ischemic heart disease, valvular disease, and cardio-oncology; (3) to
                                                               explore the potential utility of speckle-tracking echocardiography in cardiac resynchronization and implantable cardioverter
                                                               defibrillator therapy; and (4) to outline the future directions of speckle-tracking echocardiography.
                                                                           Key Words: AHA Scientific Statements ◼ cardio-oncology ◼ cardiomyopathies ◼ coronary artery disease ◼ echocardiography
                                                                                                     ◼ global longitudinal strain ◼ heart valve diseases ◼ hypertrophic cardiomyopathy
                                                               A
                                                                      ssessing left ventricular (LV) systolic function is                       function such as LV ejection fraction (LVEF) are limited
                                                                      essential for diagnosing and managing cardiac dis-                        by their reliance on LV geometric assumptions, subjective
                                                                      eases. The complex 3-dimensional organization of                          reader interpretation, sensitivity to loading conditions and
                                                               the myocardial fibers of the heart, which are arranged in                        volume, and the fact that they primarily reflect a single
                                                               a helical and perpendicular orientation, enables efficient                       plane of LV motion.1
                                                               “wringing-like” ejection, complicating traditional assess-                          In contrast, 2-dimensional speckle-tracking echo-
                                                               ment. Fiber orientation varies throughout the myocardial                         cardiography (STE) measures myocardial strain, which
                                                               wall, being longitudinal in the subendocardium, trans-                           assesses myocardial deformation during contraction
                                                               verse in the midmyocardium, and oblique in the subepi-                           and relaxation in the aforementioned longitudinal, cir-
                                                               cardium.1 Traditional methods for assessing LV systolic                          cumferential, and radial planes and is expressed as a
                                                                       percentage change in myocardial length during the car-            loading conditions.7 Conversely, impaired longitudinal
CLINICAL STATEMENTS
                                                                       diac cycle. More specifically, LV global longitudinal strain      deformation of the LV has been well validated as an early
  AND GUIDELINES
                                                                       (GLS) offers superior diagnostic and prognostic value             marker of subclinical LV impairment that occurs before
                                                                       across the spectrum of cardiovascular disorders com-              overt systolic dysfunction (LVEF <50%). Clinically, LV
                                                                       pared with LVEF and is used in clinical practice for its          GLS provides superior disease-specific diagnostic, prog-
                                                                       sensitivity in detecting subclinical LV dysfunction often         nostic, and treatment insights compared with LVEF and
                                                                       before LVEF declines.2 The strengths of GLS by STE                is intimately related to subendocardial dysfunction.2 Last,
                                                                       include its angle independence, sampling of all LV wall           although LVEF remains of prognostic value in various
                                                                       segments in a given view, high feasibility and reproduc-          cardiovascular diseases, GLS strengthens this risk strati-
                                                                       ibility, and excellent spatial resolution.1,3                     fication and offers superior reliability for serial LV function
                                                                           Joint statements were issued to standardize strain            assessment, with lower intraobserver and interobserver
                                                                       imaging with STE, aiming to reduce variability and to             variability. This consistency holds even across physicians
                                                                       improve its clinical application.3,4 In addition, recom-          with varying expertise, making GLS a more dependable
                                                                       mendations for cardiac chamber quantification outlined            tool for serial monitoring of cardiac performance.8
                                                                       best practices for measurement and reporting of strain.5              A large patient-level meta-analysis has proposed a
                                                                       Given the expanding clinical utility of STE and the incre-        GLS >−16% to be the absolute threshold indicating
                                                                       mental prognostic and therapeutic value of integrating            myocardial dysfunction regardless of vendor or clini-
                                                                       GLS into clinical practice as a potential biomarker, the          cal covariates and should alert the clinician to carefully
                                                                       objectives of this scientific statement are (1) to review         assess for cardiac pathology.9 However, interpreting the
                                                                       the principles and technical aspects of STE strain imag-          assessment within the clinical context is paramount and
                                                                       ing; (2) to provide a practical, evidence-based review of         of particular importance within the “gray zone” GLS val-
                                                                       the application of STE in heart failure (HF), cardiomy-           ues of −16% to −18%, which are considered borderline
                                                                       opathies, ischemic heart disease, valvular disease, and           or low normal. Age, sex, loading conditions, and obesity
                                                                       cardio-oncology; (3) to explore the potential utility of STE      are the most prevalent clinical modifiers to GLS that
                                                                       in cardiac resynchronization and implantable cardioverter         must be accounted for. Although the American Society
                                                                       defibrillator therapy; and (4) to outline the future direc-       of Echocardiography/European Association of Cardio-
                                                                       tions of STE.                                                     vascular Imaging Strain Standardization Task Force has
                                                                                                                                         actively worked toward harmonizing GLS measurements
                                                                                                                                         across vendors and software platforms, full standard-
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                                                                       PRINCIPLES AND TECHNICAL                                          ization has not yet been achieved. GLS interpretation
                                                                       CONSIDERATIONS                                                    should thus remain context dependent and incorporate
                                                                                                                                         patient demographics, vendor-specific differences, and
                                                                       Overview of LV Anatomy, Deformation, and                          longitudinal trends.
                                                                       Mechanics
                                                                       LV deformation and mechanics can be assessed in 3
                                                                       planes of motion: longitudinal (shortening and lengthen-          Basic Principles
                                                                       ing), circumferential (shortening and lengthening), and           Contemporary LV strain assessment is most commonly
                                                                       radial (thickening and thinning) strain. As the subendo-          performed with 2-dimensional STE, whereby software
                                                                       cardial, midmyocardial, and subepicardial layers contract,        algorithms track stable kernels of myocardial speckles
                                                                       the LV shortens and twists around its long axis to trans-         (persistent artifacts) throughout the cardiac cycle. Strain
                                                                       murally disperse shearing forces and to eject a systolic          represents the maximal deformation of the tracked LV
                                                                       stroke volume. The subendocardial and subepicardial fi-           segment normalized to its original length. Correct patient
                                                                       bers are arranged in a helical orientation and obliquely to       positioning is paramount for obtaining the optimal imag-
                                                                       one another at a 60° angle, whereas the midmyocardium             ing windows for assessment, with frame rates of 40 to
                                                                       is arranged in an equatorial plane. It is important to note       90 frames per second providing appropriate resolution.3,4
                                                                       that the myocardial layers are bound by interstitium, and         Clear visualization of the endocardial borders is neces-
                                                                       dysfunctional mechanics in 1 layer will affect the trans-         sary to ensure accurate tracking and estimation of GLS,
                                                                       mural mechanics to varying degrees.6                              which is performed and averaged from the apical 4, 2,
                                                                          The subendocardial LV fibers are characterized by lon-         and 3-chamber (apical long-axis) views.
                                                                       gitudinal motion, the midmyocardium by circumferential               Although the layered helical myocardial architecture
                                                                       motion, and the subepicardium by longitudinal and cir-            prompts consideration of multilayer strain relevance, full
                                                                       cumferential torsional deformation. The LV maintains a            (midwall) GLS currently predominates in clinical echo-
                                                                       normal ejection fraction in many pathological conditions,         cardiography. Transmural strain differences between
                                                                       given that this measure of systolic function is strongly          the subendocardial and subepicardial layers are smaller
                                                                       affected by the interplay between circumferential and             for longitudinal strain compared with radial and circum-
                                                                       radial LV mechanics, geometry, wall thickness, and                ferential strains. In addition, the myocardial layers are
mechanically tethered, and echocardiographic lateral exists, a dedicated task force comprising cardiovascu-
                                                                                                                                                                                                                       CLINICAL STATEMENTS
                                                               resolution is insufficient to differentiate layer-specific                   lar imaging experts and industry representatives has
                                                                                                                                                                                                                         AND GUIDELINES
                                                               longitudinal strain reliably, with no consistent differential                made significant progress in standardizing the software,
                                                               findings between normal and infarcted segments across                        reporting, and interpretation of cardiac deformation im-
                                                               multiple vendors.10 Thus, there is insufficient evidence to                  aging.3–5 One important caveat when interpreting GLS
                                                               recommend layer-specific LV strain for routine clinical                      across vendors is whether tracking was applied to the LV
                                                               use, and full midwall GLS remains the most preferred                         endocardium only compared with full-wall thickness.4,7,9
                                                               approach.5                                                                   Longitudinal myocardial fibers predominate in the suben-
                                                                   In the selection of the region of interest for strain                    docardium, and with the additive effect of the ellipsoid LV
                                                               assessment, it is prudent to avoid apical foreshorten-                       geometry, tracking only in this layer overestimates GLS.
                                                               ing (overestimation of GLS due to geometric distortion                       As previously mentioned, the 3 myocardial layers are
                                                               and the apparent hypercontractility of the false apex)                       bound through interstitial networks, and their mechanics
                                                               and tracking of the pericardium (underestimation of                          are mutually inclusive. Thus, it is prudent to document
                                                               GLS due to tethering of the subepicardium). Abnormali-                       whether GLS is assessed through endocardium only or
                                                               ties in LV chamber geometry and wall thickness such                          full-wall tracking and to use caution when comparing
                                                               as interventricular septal bulging and asymmetric thick-                     values across vendors with differing myocardial tracking
                                                               ness may influence strain measurements. The region of                        algorithms.
                                                               interest to assess GLS should be set straight and lon-                           Cardiac event timing is required and, depending on
                                                               gitudinally, excluding focal septal bulging. However, in                     the vendor, may be performed with LV outflow tract
                                                               ventricles with asymmetric thickening in >1 continuous                       Doppler, manual or automatic selection of the aor-
                                                               wall segment, care should be taken to widen the region                       tic valve closure point, or triggering of systolic image
                                                               of interest for inclusion. If specific segments display poor                 acquisition by gating to the R wave of the ECG. The
                                                               tracking, it is critical to reimage or adjust the region of                  last option appears to be the most frequently used,
                                                               interest manually.9                                                          and care must be taken because if the R wave is not
                                                                                                                                            detected accurately, strain measurements could be mis-
                                                                                                                                            timed and inaccurate. In addition, a paced rhythm with
                                                               Common Pitfalls and Solutions                                                a prominent atrial pacer spike can be mistaken for a
                                                               A typical assessment output will include a GLS polar map,                    QRS complex and incorrectly time the strain measure-
                                                               region of interest, segmental strain values and curves,                      ments, resulting in inaccurate assessment of myocardial
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                                                               and M-mode strain depiction when applicable (Figure 1).                      deformation. A limitation of 2-dimensional STE is the
                                                               Although it is important to acknowledge that a com-                          need for consistent R-R intervals, restricting its use in
                                                               ponent of intervendor variability in GLS measurement                         arrhythmias or respiratory variations. Real-time triplane
                                                               Figure 1. Example of a longitudinal strain assessment output in a patient with normal physiology.
                                                               A, Polar longitudinal strain map depicting the peak systolic strain in each of the 17 myocardial segments, as well as the global longitudinal strain
                                                               of −21.6%. B and C, Region of interest and segmental color-coded peak systolic stain values of the apical 3-chamber left ventricular myocardial
                                                               segments. D, Color-coded strain curves of each apical 3-chamber myocardial wall segment. E, M-mode representation of the longitudinal strain.
                                                               ANT indicates anterior; ANT SEPT, anteroseptal; APLAX, apical long axis; AVC, aortic valve closure; GLS, global longitudinal strain; INF, inferior;
                                                               LAT, lateral; POST, posterior; and SEPT, septal.
                                                                                                                                                                                                                   CLINICAL STATEMENTS
                                                                                                                                                                                                                     AND GUIDELINES
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                                                               Figure 2. Summary and polar map example of left ventricular global longitudinal strain assessment.
                                                               ESC indicates European Society of Cardiology; GLS, global longitudinal strain; HCM, hypertrophic cardiomyopathy; HF, heart failure; LV, left
                                                               ventricle; LVEF, left ventricular ejection fraction; and STEMI, ST-segment–elevation myocardial infarction.
                                                               with a GLS <−16% (P<0.001) and offer insight into                           accuracy and user confidence in that unique patterns
                                                               the impact of structural changes such as apical aneu-                       identify specific pathologies and phenotypic expressions
                                                               rysms.26–28 Last, GLS polar maps improve diagnostic                         such as significant GLS impairment in the anteroseptum
                                                                       and inferoseptum for reverse curve phenotype versus                 systolic ejection, all of which rely on healthy transmural
CLINICAL STATEMENTS
                                                                       distal and apical LV impairment in the apical phenotype.            coronary blood supply. Subendocardial fibers are more
  AND GUIDELINES
                                                                       In apical hypertrophic cardiomyopathy, the hypertrophied            vulnerable to myocardial ischemia, which can signifi-
                                                                       segments may mask the overt appearance of apical an-                cantly impair cardiac function. In acute ischemic condi-
                                                                       eurysms, which can be recognized by their dyskinetic                tions, these fibers exhibit evidence of decreased systolic
                                                                       motion and “blueberry-on-top” GLS polar map pattern.29              longitudinal shortening and postsystolic shortening after
                                                                                                                                           closure of the aortic valve.36 The myocardial injury often
                                                                                                                                           manifests in the setting of preserved circumferential
                                                                       Cardiac Amyloidosis                                                 shortening and LVEF, resulting in regional LV deforma-
                                                                       Infiltrative cardiomyopathy is characterized by the depo-           tional dysfunction (Figure 2).
                                                                       sition of abnormal proteins, granulomas, and mineral ele-
                                                                       ments, among other substances within the myocardium,
                                                                       resulting in progressive fibrosis and restrictive physiology.       Regional LV Deformation, Systolic Lengthening,
                                                                       In cardiac amyloidosis, amyloid fibril deposition in the myo-       and Postsystolic Shortening
                                                                       cardium affects longitudinal deformation, resulting in dys-         Techniques such as STE-derived GLS allow a more nu-
                                                                       functional mechanics.30 A hallmark of cardiac amyloidosis           anced evaluation of regional myocardial deformation.
                                                                       is the “apical-sparing” strain pattern, characterized by re-        GLS is particularly effective in identifying regional ab-
                                                                       duced longitudinal strain in the basal and mid-LV segments          normalities in myocardial function at rest and stress
                                                                       with preservation at the apex. It is hypothesized to result         that may not be apparent through conventional imaging
                                                                       from greater basal LV apoptosis and wall stress attribut-           methods, and its reproducibility in patients with ischemic
                                                                       able to a larger regional chamber radius, greater interstitial      heart disease surpasses that of LVEF. A study of 47 pa-
                                                                       space expansion at the basal LV territory, and a complex            tients with recent acute coronary syndrome compared
                                                                       myocyte orientation at the apex. The relative apical sparing        the assessment of GLS and LVEF between expert and
                                                                       is quantified as apical/(basal+mid) longitudinal strain, and        trainee echocardiographers and showed excellent cor-
                                                                       a ratio >1 has been shown to predict cardiac amyloidosis            relation in GLS measures regardless of experience (in-
                                                                       with a sensitivity and specificity of 93% and 82%, respec-          traclass correlation coefficient, 0.89; r=0.94) relative to
                                                                       tively (area under the curve, 0.94 [95% CI, 0.89–0.99]).31          LVEF (intraclass correlation coefficient, 0.74; r=0.71,
                                                                       An apical longitudinal strain >−14.5% has also been pro-            P<0.0001).37
                                                                       posed as a threshold for marked increase in major adverse
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                                                                                                                                                                                                                          CLINICAL STATEMENTS
                                                                                                                                                                                                                            AND GUIDELINES
                                                               Figure 3. Utility of individual segmental longitudinal strain curve analysis.
                                                               A, A patient with ischemic heart disease exhibiting both systolic lengthening (blue curve with early positive longitudinal strain) and postsystolic
                                                               shortening (purple curve with peak longitudinal stain occurring well after aortic valve closure and nearly double the value of systolic strain). B,
                                                               A patient with significant left ventricular electromechanical dyssynchrony (variable peak longitudinal strain of the 6 myocardial segments of the
                                                               specific view denoted by individual white arrows) and markedly increased mechanical dispersion (peak strain SD [PSD], 108 milliseconds). AVC
                                                               indicates aortic valve closure.
                                                               enhance standard echocardiographic parameters used in                           Surveillance of LVEF has been the main parameter
                                                               evaluating for myocardial ischemia. GLS has been shown                       for identifying LV dysfunction and defining cardiotoxicity.
                                                               to be an important predictor of postdischarge adverse                        CTRCD is commonly defined as an absolute 5% LVEF
                                                               outcomes in patients with ST-segment–elevation myo-                        reduction in symptomatic patients or a 10% decrease to
                                                                cardial infarction. In 1041 patients with ST-segment–                      <53% in asymptomatic patients. Early detection relies on
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                                                                elevation myocardial infarction with a mean LVEF of                         serial echocardiography to detect LVEF decline before
                                                                47±9% treated with percutaneous coronary interven-                          HF symptoms. However, LVEF has limitations, includ-
                                                                tion, a GLS >−15% independently predicted LV dilata-                        ing measurement variability, and is a late indicator, often
                                                                tion and adverse remodeling at 6 months (P<0.001).40                        leading to suboptimal LV recovery even with cardiopro-
                                                                At a midterm follow-up of 5 years in 1060 patients with                     tective therapy.44 A large body of literature supports the
                                                                ischemic heart disease and prior myocardial infarction, a                   diagnostic and predictive value of STE-assessed GLS
                                                                baseline GLS >−11.5% was predictive of poor survival,                       in patients receiving potentially cardiotoxic therapy. As
                                                                with each 5% relative change increasing risk by 1.6-fold                    a result, guidelines, including the 2022 European Soci-
                                                                (P<0.001).41 In patients with non–ST-segment–elevation                      ety of Cardiology guidelines on cardio-oncology, recom-
                                                                myocardial infarction, an impaired GLS of >−16.5% ef-                       mend incorporating GLS into the evaluation of patients
                                                                fectively identifies severe coronary obstruction, defined                   throughout potentially cardiotoxic cancer therapy45
                                                                as obstructive lesions of >70%. The degree of GLS im-                       (Figure 2).
                                                                pairment directly correlates with the number of involved
                                                                coronary arteries, enhancing risk stratification.42
                                                                                                                                            Value of GLS Before, During, and After Cancer
                                                                                                                                            Therapy
                                                               CARDIO-ONCOLOGY                                                              Baseline GLS can identify high-risk patients and im-
                                                               LV Functional Assessment and Cancer Therapy                                  ply prognosis in those receiving anthracycline therapy.
                                                               Many anticancer agents are linked to cardiovascular                          One study developed a baseline risk score model for
                                                               side effects, most commonly LV dysfunction and HF,                           predicting HF in patients with acute leukemia after an-
                                                               collectively called cancer therapeutics–related cardiac                      thracycline treatment, demonstrating that GLS >−15%
                                                               dysfunction (CTRCD). Given the impact of CTRCD on                            correlated more strongly with HF risk than an LVEF
                                                                                                                                            
                                                               treatment and prognosis, current strategies focus on                         <50%. In addition, a GLS >−15% was independently
                                                               early detection and intervention to minimize myocardial                      associated with all-cause mortality after adjustment for
                                                               injury during continued oncology care. Echocardiography                      age and leukemia type (P<0.001), whereas cardiovas-
                                                               is crucial in clinical decision-making before, during, and                   cular disease and baseline LVEF <50% were not.46 GLS
                                                               after cancer therapy (Figure 4).43                                           is particularly useful for patients with LVEF in the lower
                                                                       Figure 4. Utility of global longitudinal strain before, during, and after the use of cancer therapeutic agents.
                                                                       CPT indicates cardioprotective therapy; HF, heart failure; LV, left ventricle; and LVEF, left ventricular ejection fraction.
                                                                       limits of normal, between 50% and 59%, providing in-                         follow-up LVEF (59±5% versus 55±6%; P<0.0001)
                                                                       cremental prognostic value in predicting HF and overall                      compared with patients receiving standard care. Thus,
                                                                       mortality after anthracycline therapy.                                       cardioprotective therapy for isolated GLS changes ap-
                                                                           Changes in GLS are well documented in patients                           pears to be linked to less LVEF decline during anthracy-
                                                                       receiving anthracyclines, anti–human epidermal growth                        cline treatment in at-risk patients.
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                                                                       factor receptor 2 therapy such as trastuzumab, or both. A                        CTRCD can manifest years after treatment, particularly
                                                                       meta-analysis of 21 studies involving 1782 patients with                     after anthracycline therapy or radiotherapy. The St. Jude
                                                                       various cancer diagnoses found that both absolute and                        Lifetime Cohort Study found that 31.8% of long-term
                                                                       relative GLS decreases during treatment predict subse-                       adult survivors of childhood cancers treated with anthra-
                                                                       quent CTRCD. Notably, the identified cutoff values for                       cyclines, chest radiation, or both exhibited cardiac dys-
                                                                       GLS varied as a result of differences in sample sizes,                       function, indicated by decreased GLS, at a median of 23
                                                                       CTRCD definitions, and potential publication bias. A rela-                   years after diagnosis. Notably, 28% of survivors with nor-
                                                                       tive 15% worsening in GLS is generally considered clini-                     mal LVEF showed cardiac dysfunction according to GLS,
                                                                       cally significant and indicates subclinical LV dysfunction.                  which was strongly linked to prior treatment exposure.49
                                                                       These studies collectively confirm the prognostic value
                                                                       of GLS for cardiac dysfunction in patients treated with
                                                                       anthracyclines, trastuzumab, or both.47                                      VALVULAR HEART DISEASE
                                                                                                                                                    Valvular heart disease is characterized by progressive
                                                                                                                                                    hemodynamic derangements in preload and afterload.
                                                                       Role of GLS in Guiding Cardioprotection and
                                                                                                                                                    LVEF is a key metric for determining the timing of inter-
                                                                       Late Follow-Up of Patients With Cancer                                       vention; however, its sensitivity to geometric factors and
                                                                       The role of GLS in guiding cardioprotective treatment dur-                   cardiac loading conditions makes interpretation challeng-
                                                                       ing cardiotoxic therapy was explored in the SUCCOUR-                         ing. Assessment of GLS in valvular heart disease allows
                                                                       MRI trial (Strain Surveillance during Chemotherapy for                       the detection of subclinical LV dysfunction, particularly in
                                                                       Improving Cardiovascular Outcomes) that included 355                         patients with aortic and mitral regurgitation (MR) and AS,
                                                                       patients, the majority of whom were women with breast                        which supports timely intervention and improves patient
                                                                       cancer.48 This randomized trial assessed the benefits                        outcomes (Figure 2).
                                                                       of neurohormonal blockade in those with isolated GLS
                                                                       decline and no significant LVEF change during anthracy-
                                                                        cline treatment. Patients receiving cardioprotective medi-                  Aortic Stenosis
                                                                        cal therapy experienced less LVEF decline at 12 months                      In AS, LV pressure overload triggers compensatory hy-
                                                                        (−2.5±5.4% versus −5.6±5.9%; P=0.009) and higher                            pertrophy to normalize wall stress, often resulting in
preserved LVEF despite myocardial damage. Studies with severe secondary MR, GLS has been shown to re-
                                                                                                                                                                                                      CLINICAL STATEMENTS
                                                               have demonstrated the utility of GLS in detecting sub-              flect LV dysfunction more accurately than LVEF, although
                                                                                                                                                                                                        AND GUIDELINES
                                                               clinical LV dysfunction and associated clinical risk in AS.         larger studies on its clinical utility are warranted.56 Last,
                                                               In a meta-analysis of 10 studies including 1067 asymp-              in 155 patients with symptomatic severe MR and pre-
                                                               tomatic patients with significant AS and LVEF ≥50%, im-             served LVEF undergoing transcatheter edge-to-edge
                                                               paired LV GLS was associated with a 2.5-fold increase               repair, a preprocedural GLS of >−14.5% conferred a
                                                               in all-cause mortality risk, with an optimal cutoff value of        higher 1-year mortality independently of MR cause and
                                                               >−14.7% (P<0.0001).50                                               Society of Thoracic Surgeons risk score (P<0.001), pro-
                                                                   With AS progression, the increased wall stress leads            viding incremental prognostic value and identifying pa-
                                                               to diffuse interstitial collagen accumulation, evolving from        tients at higher risk.57
                                                               reactive to replacement interstitial fibrosis. Both LV mass
                                                               and myocardial fibrosis, detected with cardiac magnetic
                                                               resonance (CMR) imaging, are independently associated               CRT AND IMPLANTABLE CARDIOVERTER
                                                               with impaired GLS and portend adverse cardiovascu-                  DEFIBRILLATOR THERAPY
                                                               lar outcomes. In 261 patients with moderate to severe               In patients with cardiomyopathy meeting appropriate
                                                               AS and preserved LVEF, a GLS >−15% predicted LV                     criteria, CRT and implantable cardioverter defibrillators
                                                               replacement fibrosis with 95% sensitivity independently             are recommended by societal guidelines for the primary
                                                               of clinical risk factors, AS severity, and echocardiographic        and secondary prevention of ventricular arrhythmias and
                                                               measures of LV mass and filling pressure (P<0.001).51               sudden cardiac death and to improve electromechanical
                                                               Last, patients with moderate AS and preserved LVEF                  function of the LV in the setting of symptomatic HF and
                                                               >50% but impaired GLS >−16% have been observed to                   maximal guideline-directed medical therapy. The use of
                                                               have a 2-fold increased risk of mortality, which is similar         STE has proved invaluable in further understanding the
                                                               to that of patients with an impaired LVEF <50%, high-               complex pathophysiology across the spectrum of car-
                                                               lighting the sensitivity of GLS assessment (P<0.001).52             diomyopathic causes and provides useful measures for
                                                                                                                                   clinical prognostication and for predicting response to
                                                                                                                                   CRT and LV reverse remodeling.
                                                               Aortic Regurgitation                                                    When GLS is assessed by STE, the measure of LV
                                                               Chronic severe aortic regurgitation (AR) leads to LV vol-           mechanical dispersion is calculated as the SD of the time
                                                               ume overload, resulting in eccentric hypertrophy and LV
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                                                                       number of patients experiencing LV reverse remodeling              of its relative independence from acoustic windows,
CLINICAL STATEMENTS
                                                                       (70% versus 55%; P=0.03), higher incidence of clinical             larger fields of view, and ability to discern myocardial
  AND GUIDELINES
                                                                       improvement by ≥1 functional classes (83 versus 65%;               scarring and fibrosis. CMR feature tracking and tag-
                                                                       P=0.003), and greater freedom from death or HF hos-                ging show good overall agreement with STE for GLS
                                                                       pitalization (P=0.03) at the midterm follow-up. Similar            and circumferential strain, and CMR outperforms STE
                                                                       findings were reported in the STARTER trial (Speckle               in detecting regional strain in infarcted myocardium.66
                                                                       Tracking Assisted Resynchronization Therapy for Elec-              However, CMR feature tracking has longer acquisition
                                                                       trode Region) of 187 patients randomized to radial STE-            times, poorer spatial and temporal resolution, significant
                                                                       guided compared with fluoroscopic lead implantation,               intervendor variability, and lower strain values compared
                                                                       in which the benefit appeared magnified with a more                with STE. It also relies on endocardial and epicardial
                                                                       narrowed QRS interval ≤159 milliseconds (P=0.004).61               contours rather than intramyocardial speckles, leading
                                                                       Thus, when a CRT device is implanted, an STE-guided                to high segmental strain variability that limits clinical
                                                                       approach using radial strain may allow more precise site           use. The high cost and limited availability of CMR and
                                                                       selection for LV pacing to enhance reverse remodeling              patient factors such as claustrophobia and prohibitive
                                                                       and to improve electromechanical synchrony. The mea-               device implantations also restrict its widespread appli-
                                                                       sure of LV mechanical dispersion as part of the GLS                cation. Normal reference values for CMR strain imaging
                                                                       assessment allows quantitative assessment of this latter           are essential before widespread clinical implementation.
                                                                       point.                                                                 The development of 3-dimensional echocardiog-
                                                                                                                                          raphy is being expanded to STE, which may enable a
                                                                                                                                          more accurate assessment of myocardial strain. Unlike
                                                                       SUMMARY AND FUTURE DIRECTIONS                                      2-dimensional STE, which relies on multiple planes and
                                                                       As the field of cardiac imaging rapidly evolves, it is im-         may miss out-of-plane motion as a result of ventricular
                                                                       portant to identify future directions with regard to STE.          twisting, 3-dimensional STE captures all strain com-
                                                                       It is important to note that the interest in and efforts to        ponents—longitudinal, circumferential, and radial—in 1
                                                                       integrate LV strain assessment as a routine and standard           acquisition, better reflecting the complex 3-dimensional
                                                                       practice across echocardiography laboratories are grow-            organization of myocardial fibers, reducing acquisi-
                                                                       ing. By identifying early or subclinical LV dysfunction,           tion time, and providing dynamic GLS polar maps
                                                                       strain imaging will allow individual treatment planning,           while minimizing nonmyocardial speckle interference.
                                                                       optimization of timing for interventions, and nuanced risk         However, the lower spatial and temporal resolution of
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                                                                       stratification. Impaired LV GLS consistently shows an in-          3-dimensional STE can limit tracking reliability, particu-
                                                                       dependent association with adverse outcomes, justifying            larly for segmental analysis, and current limitations may
                                                                       its current use for risk stratification. However, outside of       underestimate 3-dimensional global strain compared
                                                                       HF and CTRCD, evidence supporting the use of GLS                   with 2-dimensional values, posing ongoing challenges.9
                                                                       to guide specific changes in clinical management is still              Continued research and outreach by STE experts
                                                                       evolving.                                                          and collaborations between vendors have enabled sig-
                                                                           Machine-learning algorithms have shown that auto-              nificant advancements in identifying normative strain
                                                                       mated measurement of LV GLS may be performed within                values across different populations, accounting for
                                                                       8 seconds, which would support easy routine integra-               sex, age, and ethnicity, and have significantly improved
                                                                       tion into laboratory workflow.62 Artificial intelligence and       intervendor comparability. As the interest in and clini-
                                                                       deep learning enhance STE, with automated GLS and                  cal comfort with STE grow, so will its role in assessing
                                                                       regional strain showing good agreement with conven-                the impact of the heart on cardiovascular (congenital
                                                                       tional methods, accurately identifying subtle LV dysfunc-          heart disease, myocarditis, inflammatory disorders) and
                                                                       tion, and offering rapid, vendor-agnostic results with less        noncardiovascular (chronic kidney disease, sepsis, pul-
                                                                       variability. Future validation and prognostic refinement of        monary disorders) conditions, which will further expand
                                                                       artificial intelligence–derived strain promise to elevate its      the use of this modality in everyday medical practice. An
                                                                       clinical impact, making it a widely accessible tool for per-       in-depth, multidisciplinary, stepwise recommendation of
                                                                       sonalized care.63–65 Nevertheless, it is acknowledged that         STE is needed to further the modality and to highlight its
                                                                       challenges persist in educating nonimaging cardiolo-               importance in the assessment of myocardial function.
                                                                       gists and internal medicine physicians unfamiliar with the
                                                                       interpretation of strain imaging, necessitating structured
                                                                       training, workshops, and specialist-clinician collaboration        ARTICLE INFORMATION
                                                                       to boost adoption.                                                 The American Heart Association makes every effort to avoid any actual or poten-
                                                                           CMR imaging techniques such as feature tracking                tial conflicts of interest that may arise as a result of an outside relationship or a
                                                                                                                                          personal, professional, or business interest of a member of the writing panel. Spe-
                                                                       and tagging offer alternative approaches to STE for
                                                                                                                                          cifically, all members of the writing group are required to complete and submit a
                                                                       the assessment of LV strain. There is particular value             Disclosure Questionnaire showing all such relationships that might be perceived
                                                                       in CMR when assessing cardiomyopathies because                     as real or potential conflicts of interest.
                                                                   This statement was approved by the American Heart Association Sci-                       the American Heart Association. Circulation. 2025;152:e•••–e•••. doi: 10.1161/
                                                               ence Advisory and Coordinating Committee on June 5, 2025, and the                            CIR.0000000000001354
                                                                                                                                                                                                                                                    CLINICAL STATEMENTS
                                                               American Heart Association Executive Committee on June 18, 2025. A                                The expert peer review of AHA-commissioned documents (eg, scientific
                                                                                                                                                                                                                                                      AND GUIDELINES
                                                               copy of the document is available at https://professional.heart.org/state-                   statements, clinical practice guidelines, systematic reviews) is conducted by the
                                                               ments by using either “Search for Guidelines & Statements” or the “Browse                    AHA Office of Science Operations. For more on AHA statements and guidelines
                                                               by Topic” area. To purchase additional reprints, call 215-356-2721 or email                  development, visit https://professional.heart.org/statements. Select the “Guide-
                                                               Meredith.Edelman@wolterskluwer.com                                                           lines & Statements” drop-down menu, then click “Publication Development.”
                                                                   The American Heart Association requests that this document be cited as fol-                   Permissions: Multiple copies, modification, alteration, enhancement, and dis-
                                                               lows: Mihos CG, Liu JE, Anderson KM, Pernetz MA, O’Driscoll JM, A    urigemma GP,           tribution of this document are not permitted without the express permission of the
                                                               Ujueta F, Wessly P; on behalf of the American Heart Association Council on Pe-               American Heart Association. Instructions for obtaining permission are located at
                                                               ripheral Vascular Disease; Council on Cardiovascular and Stroke Nursing; and                 https://www.heart.org/permissions. A link to the “Copyright Permissions Request
                                                               Council on Clinical Cardiology. Speckle-tracking strain echocardiography for the             Form” appears in the second paragraph (https://www.heart.org/en/about-us/
                                                               assessment of left ventricular structure and function: a scientific statement from           statements-and-policies/copyright-request-form).
                                                               Disclosures
                                                               Writing Group Disclosures
                                                                Jennifer E.     Memorial Sloan Kettering            None                                       None        None            None         None           Cytel*           None
                                                                Liu             Cancer Center
                                                                Jamie M.        Diabetes Research Centre,           None                                       None        None            None         None           None             None
                                                                O’Driscoll      College of Life Sciences,
                                                                                University of Leicester (United
                                                                                Kingdom)
                                                                Maria           Self-employed                       None                                       None        None            None         None           None             None
                                                                Alexandra
                                                                Pernetz
                                                                Francisco       Brigham and Women’s                 None                                       None        None            None         None           None             None
                                                                Ujueta          Hospital
                                                                  This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the
                                                               Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be “significant” if (a) the person
                                                               receives $5000 or more during any 12-month period, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock or share of the
                                                               entity, or owns $5000 or more of the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition.
                                                                  *Modest.
                                                                  †Significant.
Reviewer Disclosures
                                                                                                                                                                                                                       Consultant/
                                                                                                                                              Other research       Speakers’ bureau/       Expert       Ownership      advisory
                                                                Reviewer       Employment                  Research grant                     support              honoraria               witness      interest       board            Other
                                                                Jose           University of Colorado      None                               None                 None                    None         None           None             None
                                                                Banchs
                                                                Thomas H.      Baker Heart and             National Health and                None                 None                    None         None           None             None
                                                                Marwick        Diabetes Institute          Medical Research Council
                                                                               (Australia)                 (grants including the use of
                                                                                                           myocardial strain)*
                                                                Denisa         Istituto Auxologico         None                               None                 GE Healthcare*;         None         None           None             None
                                                                Muraru         Italiano, IRCCS (Italy)                                                             Philips*
(Continued )
                                                                                                                                                                                                                             Consultant/
  AND GUIDELINES
                                                                          This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Ques-
                                                                       tionnaire, which all reviewers are required to complete and submit. A relationship is considered to be “significant” if (a) the person receives $5000 or more during any
                                                                       12-month period, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $5000 or more of
                                                                       the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition.
                                                                          *Modest.
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