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40765507

This scientific statement from the American Heart Association discusses the use of speckle-tracking strain echocardiography for assessing left ventricular (LV) structure and function, highlighting its advantages over traditional ejection fraction methods. It emphasizes the superior diagnostic and prognostic value of global longitudinal strain (GLS) in detecting subclinical LV dysfunction and outlines the principles, applications, and future directions of this imaging technique. The statement aims to standardize strain imaging practices and improve clinical outcomes in various cardiovascular conditions.
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0% found this document useful (0 votes)
14 views14 pages

40765507

This scientific statement from the American Heart Association discusses the use of speckle-tracking strain echocardiography for assessing left ventricular (LV) structure and function, highlighting its advantages over traditional ejection fraction methods. It emphasizes the superior diagnostic and prognostic value of global longitudinal strain (GLS) in detecting subclinical LV dysfunction and outlines the principles, applications, and future directions of this imaging technique. The statement aims to standardize strain imaging practices and improve clinical outcomes in various cardiovascular conditions.
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
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Circulation

AHA SCIENTIFIC STATEMENT

Speckle-Tracking Strain Echocardiography for


the Assessment of Left Ventricular Structure
and Function: A Scientific Statement From the
American Heart Association
Christos G. Mihos, DO, Vice Chair; Jennifer E. Liu, MD; Kelley M. Anderson, PhD, RN, FNP;
Maria Alexandra Pernetz, RDCS, RVT, RCCS, ACS; Jamie M. O’Driscoll, PhD; Gerard P. Aurigemma, MD;
Francisco Ujueta, MD, FAHA; Priscilla Wessly, MD, Chair; on behalf of the American Heart Association Council on Peripheral
Vascular Disease; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology

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,
Downloaded from http://ahajournals.org by on August 11, 2025

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

© 2025 American Heart Association, Inc.


Circulation is available at www.ahajournals.org/journal/circ

Circulation. 2025;152:e00–e00. DOI: 10.1161/CIR.0000000000001354 TBD TBD, 2025 e1


Mihos et al STE for Assessing LV Structure and Function

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

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Mihos et al STE for Assessing LV Structure and Function

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.

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Mihos et al STE for Assessing LV Structure and Function

echocardiography with a matrix probe overcomes this Preclinical HF


CLINICAL STATEMENTS

by acquiring 3 simultaneous LV views from a single


Preclinical HF, defined as stage B, offers a key opportu-
AND GUIDELINES

cycle. Last, to reduce motion artifacts and to improve


nity for early intervention. According to the 2022 Ameri-
image quality, the patient is asked to inhale or exhale
can Heart Association/American College of Cardiology
and hold their breath while the images are acquired.
guidelines, a GLS value >−16% in the setting of LVEF
Capturing 3 consecutive beats ensures that the data
>50% is recommended for diagnosing stage B HF.18
are reliable and reproducible.
GLS provides prognostic value in preclinical HF by iden-
Documentation of the systemic blood pressure at
tifying subclinical myocardial dysfunction before the on-
the time of strain assessment is important because
set of overt symptoms and may reclassify the HF stage
GLS can be attenuated by increased afterload, par-
in up to 14% of patients.19
ticularly in patients with hypertension, aortic steno-
sis (AS), and hypertrophic cardiomyopathy.9 Indeed, HF With Preserved Ejection Fraction
experimental models using graded aortic banding have HFpEF, in which LVEF remains ≥50%, accounts for
shown a moderate relationship between increasing LV >50% of HF cases.18 The European Society of Cardi-
wall stress and worsening GLS (r=0.68, P<0.005) and ology guidelines acknowledge GLS >−16% as a minor
radial strain (r=0.5, P=0.02), although to a lesser extent ­diagnostic criterion for HFpEF.17 This is of paramount
than impacts classically observed on LVEF.11 Akin to utility, given the overlap of HFpEF and noncardiac causes
LV ­ pressure-volume loops, integrating the systemic of dyspnea in terms of clinical presentation, which often
blood pressure as measured by the brachial artery cuff delays diagnosis. Analyses from randomized controlled
pressure with GLS produces a stress-strain loop that trials have correlated impaired GLS in HFpEF with in-
estimates the global and regional LV myocardial work creased LV stiffness, elevated NT-proBNP (N-terminal
performed. This novel echocardiographic parameter pro-B-type natriuretic peptide) levels, and greater ad-
was designed to resolve whether GLS reduction is due verse cardiovascular outcomes independently of estab-
to reduced contractility (reflected as reduced myocar- lished clinical risk factors.20,21
dial work) or increased afterload (reflected as increased
myocardial work).
For accurate LV myocardial work analysis, the bra- HF With Reduced Ejection Fraction
chial artery cuff pressure is measured immediately after In HF with reduced ejection fraction, GLS offers pre-
recording of the apical views, with the patient supine and
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dictive accuracy that exceeds LVEF in terms of mortal-


relaxed with the arm at the level of the heart, to avoid ity and hospitalizations.22–24 In a study of 1065 patients
overestimation from prestudy blood pressure (eg, emo- with HF with reduced ejection fraction, each 1% abso-
tional stress) or underestimation in the left lateral posi- lute decrease in GLS conferred a 15% increased risk of
tioning (eg, arm height).12 Myocardial work parameters all-cause mortality (P=0.008), with the worst outcomes
have been shown to discriminate coronary ischemia and among men with atrial fibrillation.22 Worsening GLS cor-
to predict a positive response to cardiac resynchroniza- relates with LV remodeling, progression of diastolic dys-
tion therapy (CRT).13–15 From a physiological standpoint, function, and worsening functional class, with a cutoff
myocardial work indices reflect cellular glucose metabo- of >−6.95% associated with >2-fold increased risk of
lism, oxygen consumption, and tissue fibrosis, offering a adverse cardiovascular events regardless of an ischemic
promising adjunct modality to LV performance assess- or nonischemic substrate (P=0.01).23
ment as clinical experience and intervendor development
progress.16
Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy is a heterogeneous dis-
HF AND CARDIOMYOPATHIES order characterized by LV hypertrophy, myocardial fiber
HF is a complex syndrome characterized by structural or disarray, and extensive fibrosis. In early or mild pheno-
functional cardiac abnormality and corroborated by el- typic stages, distinguishing hypertrophic cardiomyopa-
evated natriuretic peptide levels or objective evidence of thy from other causes of hypertrophy is challenging with
pulmonary or systemic congestion.17 Echocardiography important clinical implications. It is important to note
remains the standard diagnostic tool for categorizing HF that a GLS of >−14.3% can differentiate hypertrophic
according to LVEF. However, LVEF has important limita- cardiomyopathy from hypertensive heart disease or ath-
tions such as observer variability and geometric assump- letic remodeling with a sensitivity, specificity, and pre-
tions, particularly in HF with preserved ejection fraction dictive ­accuracy of 77%, 97%, and 87%, respectively
(HFpEF). In HF populations, GLS has emerged as an (P<0.001).25 GLS and myocardial work indices provide
important metric for detecting subclinical myocardial excellent risk stratification in hypertrophic cardiomyopa-
dysfunction, differentiating pathological conditions, and thy, with a GLS >−10% increasing the occurrence of
monitoring therapeutic responses (Figure 2). major adverse cardiovascular events 4-fold compared

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Mihos et al STE for Assessing LV Structure and Function

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

Circulation. 2025;152:e00–e00. DOI: 10.1161/CIR.0000000000001354 TBD TBD, 2025 e5


Mihos et al STE for Assessing LV Structure and Function

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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In the analysis of individual LV segmental strain


cardiovascular events in a cohort of mixed amyloidosis curves, the observance of systolic lengthening informs
subtypes.30 Although most prevalent in cardiac amyloido- the presence of ischemic myocardium, whereby affected
sis (74%), a degree of apical sparing may occur in up to myocardial segments elongate during systole as a result
44% of patients with AS, highlighting the importance of of ineffective contraction, dyskinetic motion caused by
integrating ancillary echocardiographic findings and clini- abnormal energetics, or transmural scarring. Similarly,
cal context.32 In addition, the presence of chronic kidney postsystolic shortening occurs when LV segments con-
disease may reduce the specificity of GLS in detecting car- tract after the primary systolic phase, often seen in isch-
diac amyloidosis with the apical-sparing pattern.33 emic myocardium (Figure 3A). In a prospective study of
293 patients with suspected angina, postsystolic short-
Anderson-Fabry Disease ening was an independent predictor of obstructive coro-
nary artery disease and conferred a 2.5-fold increased
Anderson-Fabry disease is a lysosomal storage disorder risk of adverse cardiovascular events (P=0.03).38 Given
characterized by accumulation of intracellular glycosphin- their utility, the 2024 European Society of Cardiology
golipids, including infiltration within the myocardium. Pa-
guidelines for the management of chronic coronary
tients with Anderson-Fabry disease often present with syndromes recommend strain imaging for detecting
concentric LV and papillary muscle hypertrophy. Impaired decreased systolic shortening or GLS, early systolic
GLS is associated with a higher incidence of major adverse lengthening, or postsystolic shortening in patients with
cardiovascular events compared with preserved GLS, with normal LV function and a clinical suspicion of coronary
a cutoff of −14.1% proposed as a robust threshold.34 Po- artery disease.39
lar maps with impaired GLS predominating in the basal to
midlateral and posterior LV territory are often noted.35
Acute and Chronic Coronary Syndromes
Incorporating STE and GLS into the early assessment
ISCHEMIC HEART DISEASE of acute coronary syndromes identifies patients who
As noted here, LV mechanics are facilitated by the intri- could benefit from early invasive management in that
cate helical structure of the myocardial fibers that sup- the aforementioned use of segmental strain curve analy-
port coordinated chamber contraction, relaxation, and ses and interpretation of GLS polar maps can markedly

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Mihos et al STE for Assessing LV Structure and Function

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

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Mihos et al STE for Assessing LV Structure and Function
CLINICAL STATEMENTS
AND GUIDELINES

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.
Downloaded from http://ahajournals.org by on August 11, 2025

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

e8 TBD TBD, 2025 Circulation. 2025;152:e00–e00. DOI: 10.1161/CIR.0000000000001354


Mihos et al STE for Assessing LV Structure and Function

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
Downloaded from http://ahajournals.org by on August 11, 2025

to peak longitudinal strain in each of the 17 myocardial


dilatation to attenuate wall stress. Once the patient is wall segments analyzed (Figure 3B). Mechanical disper-
symptomatic or LVEF declines, survival decreases sig- sion quantifies the temporal heterogeneity in electro-
nificantly without timely surgical intervention. In a pivotal mechanical activation of the LV, serving as a surrogate
study, 84% of deaths in patients with severe AR occurred for myocardial dyssynchrony and fibrosis. A mechanical
in patients with LV end-systolic diameter index <2 cm/ dispersion >60 milliseconds is generally agreed on as
m², indicating that risk increases even before overt LV re- the threshold for abnormal, identifies across cardiomyo-
modeling.53 In 1063 patients with asymptomatic severe pathic substrates as a reproducible cutoff to predict ven-
AR, LV end-systolic diameter index <2.5 cm/m², and tricular arrhythmias, and is associated with mortality risk
LVEF >50%, each unit of worsening GLS independently in severe AS.58,59
conferred an 11% increased risk of mortality (P=0.003). Radial strain STE describes the systolic LV wall thick-
A GLS of >−19.5% was shown to mediate long-term ening that occurs as a result of longitudinal and circum-
survival, and aortic valve surgery at this threshold blunted ferential myofiber shortening and finite compressibility
mortality risk (P<0.001).54 of the myocardium. Global radial strain is measured
at the LV basal, midpapillary muscle, and apical levels
and may be further analyzed regionally or segmentally.
Mitral Regurgitation In patients with HF with reduced ejection fraction and
MR is characterized by pure volume overload, increased LVEF <35% undergoing CRT device implantation,
preload, and normal afterload, which allow LVEF to re- radial strain curves can quantify the degree of LV dys-
main normal despite underlying dysfunction. In 737 pa- synchrony and identify the latest activated myocardial
tients with asymptomatic primary severe MR, preserved segment, which may assist in selection of the optimal
LVEF, and normal LV dimensions, a GLS >−21.7% was LV pacing site. The TARGET trial (Targeted Left Ven-
associated with increased mortality, suggesting that tricular Lead Placement to Guide Cardiac Resynchro-
even “normal” GLS in severe MR is linked to poorer nization Therapy) randomized 220 patients undergoing
outcomes.55 Each unit of worsening GLS independently CRT implantation to LV lead placement guided by the
conferred a 60% increased risk of long-term mortality STE radial strain delay of the latest activated myocar-
(P<0.001), and addition of GLS to traditional risk models dial segment free from scar or fluoroscopic lead place-
improved their predictive value. In dilated cardiomyopathy ment.60 STE guidance was associated with a greater

Circulation. 2025;152:e00–e00. DOI: 10.1161/CIR.0000000000001354 TBD TBD, 2025 e9


Mihos et al STE for Assessing LV Structure and Function

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
Downloaded from http://ahajournals.org by on August 11, 2025

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.

e10 TBD TBD, 2025 Circulation. 2025;152:e00–e00. DOI: 10.1161/CIR.0000000000001354


Mihos et al STE for Assessing LV Structure and Function

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

Writing Other Speakers’ Consultant/


group research bureau/ Expert Ownership advisory
member Employment Research grant support honoraria witness interest board Other
Priscilla Aurora Cardiovascular and None None None None None None None
Wessly Thoracic Services, Aurora
Sinai/Aurora St. Luke’s
Medical Centers
Christos G. Mount Sinai Medical Center Florida Heart Research None GE None None None None
Mihos Foundation (echo research Healthcare†
on cardiac rehabilitation and
strain echocardiography)†; GE
Healthcare (echo research on
right-sided heart function and strain
echocardiography)†
Kelley M. University of Virginia School None None None None None None None
Anderson of Nursing
Gerard P. University of Massachusetts None None None None None None None
Aurigemma Medical School
Downloaded from http://ahajournals.org by on August 11, 2025

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 )

Circulation. 2025;152:e00–e00. DOI: 10.1161/CIR.0000000000001354 TBD TBD, 2025 e11


Mihos et al STE for Assessing LV Structure and Function

Reviewer Disclosures Continued


CLINICAL STATEMENTS

Consultant/
AND GUIDELINES

Other research Speakers’ bureau/ Expert Ownership advisory


Reviewer Employment Research grant support honoraria witness interest board Other
Salima Ochsner Medical None None None None None None None
Qamruddin Center
Marta Thorax Institute, None None General Electric*; General None General None
Sitges IDIBAPS, University Siemens Electric* Electric*
of Barcelona (Spain) Healthineers*;
Canon Medical*

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.

13. Lin J, Wu W, Gao L, He J, Zhu Z, Pang K, Wang J, Liu M, Wang H. Global


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e14 TBD TBD, 2025 Circulation. 2025;152:e00–e00. DOI: 10.1161/CIR.0000000000001354

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