BSE and BCOS Guideline for Transthoracic Echocardiographic

J A C C : C A R D I O O N C O L O G Y VO L . 3 , N O . 1 , 2 0 2 1

© 2 0 2 1 T H E A U T H O R S . P U B L I S H E D B Y E L S E V I E R O N B E H A L F O F T H E A M E R I C A N

C O L L E G E O F C A R D I O L O G Y F O U N D A T I O N . T H I S I S A N O P E N A C C E S S A R T I C L E U N D E R

T H E C C B Y - N C - N D L I C E N S E ( H T T P : / / C R E A T I V E C OMMON S . O R G / L I C E N S E S / B Y - N C - N D / 4 . 0 / ) .

STATE-OF-THE-ART REVIEW

BSE and BCOS Guideline forTransthoracic EchocardiographicAssessment of Adult Cancer PatientsReceiving Anthracyclinesand/or Trastuzumab
Rebecca Dobson, MBCHB (HONS), MD,a,* Arjun K. Ghosh, MBBS, MSC, PHD,b,c,* Bonnie Ky, MD, MSCE,d
Tom Marwick, MBBS, PHD, MPH,e Martin Stout, PHD,f Allan Harkness, MB CHB, MSC,g Rick Steeds, MA, MD,h

Shaun Robinson, MSC,i David Oxborough, PHD,j David Adlam, BA, BM BCH, DPHIL,k

Susannah Stanway, MB CHB, MSC, MD,l Bushra Rana, MBBS,m Thomas Ingram, MB CHB, PHD,n Liam Ring, MBBS,o

Stuart Rosen, MA, MD,p Chris Plummer, BSC, PHD, BM BCH,q Charlotte Manisty, MBBS, MA, PHD,b

Mark Harbinson, MB BCH, MMEDSCI, MD,r Vishal Sharma, MD,s Keith Pearce, BSC,f Alexander R. Lyon, MD, PHD,p

Daniel X. Augustine, MD,t on behalf of the British Society of Echocardiography (BSE) and theBritish Society of Cardio-Oncology (BCOS)

ABSTRACT

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The subspecialty of cardio-oncology aims to reduce cardiovascular morbidity and mortality in patients with cancer or

following cancer treatment. Cancer therapy can lead to a variety of cardiovascular complications, including left ventricular

systolic dysfunction, pericardial disease, and valvular heart disease. Echocardiography is a key diagnostic imaging tool in the

diagnosis and surveillance for many of these complications. The baseline assessment and subsequent surveillance of pa-

tients undergoing treatmentwith anthracyclines and/or human epidermal growth factor receptor (HER) 2-positive targeted

treatment (e.g., trastuzumab and pertuzumab) form a significant proportion of cardio-oncology patients undergoing

echocardiography. This guideline from the British Society of Echocardiography and British Cardio-Oncology Society out-

lines a protocol for baseline and surveillance echocardiography of patients undergoing treatment with anthracyclines

and/or trastuzumab. The methodology for acquisition of images and the advantages and disadvantages of techniques

are discussed. Echocardiographic definitions for considering cancer therapeutics-related cardiac dysfunction are

also presented. (J Am Coll Cardiol CardioOnc 2021;3:1–16) © 2021 The Authors. Published by Elsevier on behalf of

the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license

(http://creativecommons.org/licenses/by-nc-nd/4.0/)

N 2666-0873 https://doi.org/10.1016/j.jaccao.2021.01.011

m the aCardio-Oncology Service, Liverpool Heart and Chest NHS Foundation Trust, Liverpool, United Kingdom; bCardio-

cology Service, Barts Heart Centre, Barts Health NHS Trust, London, United Kingdom; cCardio-Oncology Service, Hatter Car-

vascular Research Institute, University College London and University College London Hospitals NHS Foundation Trust,

ndon, United Kingdom; dPerelman School of Medicine at the University of Pennsylvania, Philadelphia, USA; eBaker Heart and

betes Institute, Melbourne, Australia; fUniversity Hospital South Manchester NHS Foundation Trust, Manchester, United

gdom; gEast Suffolk and North Essex NHS Foundation Trust, Colchester, United Kingdom; hUniversity Hospitals Birmingham

S Foundation Trust, Birmingham, United Kingdom; iNorth West Anglia Foundation Trust, United Kingdom; jLiverpool John

ores University, Liverpool, United Kingdom; kUniversity Hospitals of Leicester NHS Trust, Leicester, United Kingdom; lRoyal

rsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom; mImperial College Healthcare NHS

st, London, United Kingdom; nThe Shrewsbury and Telford Hospital NHS Trust, Shrewsbury, United Kingdom; oWest Suffolk

S Foundation Trust, Bury St. Edmunds, United Kingdom; pRoyal Brompton and Harefield NHS Foundation Trust and Imperial

llege London, London, United Kingdom; qThe Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, United

gdom; rBelfast Health and Social Care Trust, Belfast, United Kingdom; sRoyal Liverpool and Broadgreen University Hospitals

S Trust, Liverpool, United Kingdom; and the tDepartment of Cardiology, Royal United Hospitals Bath NHS Foundation Trust,

http://creativecommons.org/licenses/by-nc-nd/4.0/

https://doi.org/10.1016/j.jaccao.2021.01.011

http://crossmark.crossref.org/dialog/?doi=10.1016/j.jaccao.2021.01.011&domain=pdf

http://creativecommons.org/licenses/by-nc-nd/4.0/

ABBR EV I A T I ON S

AND ACRONYMS

2D = 2-dimensional

3D = 3-dimensional

A2C = apical 2-chamber



BSE = British Society of

Echocardiography

CMR = cardiac magnetic

resonance

CTRCD = cancer therapy–

related cardiac dysfunction

ECG = electrocardiogram

GLS = global longitudinal

strain

HER2 = human epidermal

growth factor receptor 2

LV = left ventricular

LVEF = left ventricular ejection

fraction

MV = mitral valve

RH = right heart

ROI = region of interest

RV = right ventricular

TDI = tissue Doppler imaging

TRV = tricuspid regurgitant

velocity

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Dobson et al. J A C C : C A R D I O O N C O L O G Y , V O L . 3 , N O . 1 , 2 0 2 1

Cardio-Oncology Echocardiography Protocol for Anthracyclines and/or Trastuzumab M A R C H 2 0 2 1 : 1 – 1 6

2

HIGHLIGHTS

� Cardio-oncology patients account for anincreasing proportion of echocardiogra-phy requests.

� Accurate assessment of LV systolicfunction is critical to decision-making inthis patient group.

� 2D LVEF, 3D LVEF, GLS, and RV assess-ment should be used in the echocardio-graphic assessment of these patients.

� The clinical implications of a significantdecline in GLS with potentially car-diotoxic cancer therapy require furtherinvestigation.

A dvances in cancer detection andtreatment have resulted in agrowing number of cancer survivors.

Cardio-oncology is a relatively new subspe-cialty that aims to prevent, detect, monitorand treat the cardiac complications of cancertherapy (1). The goal of the cardio-oncologistis to provide optimal cardiovascular care forpatients with cancer in a multidisciplinarysetting involving oncologists, cardiologists,surgeons, cardiac physiologists/scientists,specialist nurses, pharmacists, and alliedhealth professionals (2). Cancer therapy–related cardiac dysfunction (CTRCD) is afrequently encountered clinical presenta-tion, and transthoracic echocardiography isthe cornerstone of its screening anddetection.

The British Society of Echocardiography(BSE) has recently published an updatedminimum dataset for a standard adulttransthoracic echocardiogram (3)(Supplemental Appendix). This cardio-oncology guideline is designed to be usedin conjunction with the minimum datasetand provides guidance on transthoracicechocardiographic image acquisition anddata interpretation in patients undergoingtreatment with anthracyclines and/ortrastuzumab.

This consensus guideline:

1. Defines the standard echocardiography protocolfor the assessment of left ventricular (LV) functionin those undergoing anthracyclines and/or humanepidermal growth factor receptor 2 (HER2)-tar-geted therapy.

2. Defines cardiotoxicity and specifically CTRCDwith anthracyclines and/or HER2-targetedtherapy.

3. Provides strategies to enable the acquisition ofhigh-quality echocardiography for patients un-dergoing anthracyclines and/or HER2-targetedtherapy.

4. Reviews the nonechocardiographic considerationsfor clinical decision-making; reviews risk factors

d Kingdom. *Drs. Dobson and Ghosh contributed equally to this w

er. Juan Carlos Plana Gomez, MD, served as the Guest Associate

s attest they are in compliance with human studies committe

and Food and Drug Administration guidelines, including patien

thor Center.

received June 12, 2020; revised manuscript received January 18

for cardiotoxicity; and provides guidance forreferral to a cardio-oncology service.

BACKGROUND

Anthracyclines (e.g., doxorubicin, epirubicin, dauno-rubicin, and idarubicin) and the monoclonal antibodytrastuzumab (Herceptin, Genentech, South San Fran-cisco, California) are commonly implicated in thedevelopment of LV dysfunction (4). Although there areother cardiotoxic anticancer therapies, in our experi-ence, patients receiving anthracyclines and/or trastu-zumab account for the majority of cardio-oncologyechocardiograms performed, hence are the focusof this guideline. Trastuzumab may also be prescribedin combination with pertuzumab, another HER2-pos-itive–targeted monoclonal antibody, or with emtan-sine (Kadcyla/T-DM1, Genentech), which may beassociatedwith additional cardiovascular concerns (5).

Many mechanisms are postulated to explainanthracycline-induced cardiotoxicity. Generation ofexcess reactive oxygen species and oxygen free rad-icals causing damage to deoxyribonucleic acid (DNA),ribonucleic acid (RNA), proteins, and membranelipids, and resultant cardiomyocyte death is one ofthe most commonly accepted cardiotoxicity mecha-nisms (6). The mechanisms responsible fortrastuzumab-related cardiotoxicity are less clear but

ork. Anju Nohria, MD, served as the Editor-in-Chief

Editor for this paper.

es and animal welfare regulations of the authors’

t consent where appropriate. For more information,

, 2021, accepted January 19, 2021.


https://www.jacc.org/author-center

TABLE 1 Minimum Requirements for Baseline Assessment for Patients Receiving Anthracyclines/Trastuzumab (in Addition to the Full BSE Minimum Dataset in the

Supplemental Appendix)

View (Modality) Measurement Explanatory Note Image

Vital signs Blood pressure, heart rate and rhythm

Apical 3D 3D volumes and LVEF ECG signal with clear R-wave.Adjust scanner settings to ensure optimal resolution.Ensure ROI is within the 3D volume sector. Maximize the frame rate,

adjusting number of subvolumes according to patient breath-holdingcapability as needed.

Acquire images with the probe maintained in a steady position and at end-expiration.

Before accepting acquisition, review volume and 9-slice view to ensure nostitch artifacts.

A4C/A3C/A2C GLS GLS measurement Optimal ECG signal with minimal heart rate variability should be presentacross 3 cardiac cycles.

Heart rate variability will limit the calculation of GLS values, which can beproblematic in patients with atrial fibrillation. High-quality imageacquisition, maintaining a frame rate of 40 to 90 frames/s at a normalheart rate, is key.

Clear endocardial and epicardial definition is required to ensure adequatesegmental tracking throughout the cardiac cycle. Markers are placedin each of the respective basal and apical regions, using automatedtracking where possible to maintain reproducible results. Automatedtracking should also be combined with a visual assessment of trackingin each view across the whole ROI, including the endocardial andepicardial border. If more than 2 segments in any 1 view are notadequately tracked, the calculation of GLS should be avoided.

3D ¼ 3-dimensional; A2C ¼ apical 2 chamber; A3C¼ apical 3 chamber; A4C ¼ apical 4 chamber; BSE¼ British Society of Echocardiography; ECG ¼ electrocardiogram; GLS ¼ global longitudinal strain; LVEF¼left ventricular ejection fraction; ROI ¼ region of interest.

J A C C : C A R D I O O N C O L O G Y , V O L . 3 , N O . 1 , 2 0 2 1 Dobson et al.M A R C H 2 0 2 1 : 1 – 1 6 Cardio-Oncology Echocardiography Protocol for Anthracyclines and/or Trastuzumab

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likely are related to inhibition of the neuregulin-1(NRG-1)/ErbB signaling pathway (7). Commonly, butnot in all cases, there is recovery of LV function withtrastuzumab cardiotoxicity (8).

The addition of trastuzumab to anthracyclinechemotherapy alone improves the overall survival ofpatients with HER2-positive tumors by approximately33%, with a 50% reduction in disease recurrence(9,10). For this reason, the management of cardiacdysfunction should first consider the initiation ofcardioprotective therapies, rather than withholdingprognostically important oncology treatment. Man-agement decisions require close collaboration be-tween oncology and cardiology specialists. Inaddition, the risk of cardiotoxicity is not just an issue

during oncology treatment (chemotherapy and/orradiotherapy) but can remain a concern for manyyears thereafter (11,12).

THE ROLE OF ECHOCARDIOGRAPHY AND THE

RECOMMENDED CARDIO-ONCOLOGY PROTOCOL

All patients should undergo a comprehensive base-line echocardiogram to include the BSE minimumtransthoracic dataset (Supplemental Appendix) withadditional cardio-oncology measurements (Table 1).Best practice for the minimum dataset for a targetedcardio-oncology protocol includes 2-dimensional (2D)and 3-dimensional (3D) volumes, LV ejection fraction(LVEF), global longitudinal strain (GLS), right



TABLE 2 Cardio-Oncology Targeted Echocardiogram Reporting Protocol


Vital signs Blood pressure, heart rate and rhythm

A4C andA2C 2D

Simpson’sbiplanevolumes andLVEF

Trace the endocardial border. Depending on the vendor, the MV level contour ismade by a straight line at the beginning or end of tracing. LV length is defined asthe distance between the midpoint of the MV-level line and the most distal pointof the LV apex. Take care to ensure the LV is not foreshortened. Papillary musclesand trabeculations are included in the volumes and considered part of thechamber.

Measure at end-diastole and end-systole.Volumes indexed to BSA.

Apical 3D 3D volumes andLVEF

See Table 1

A4C/A3C/A2C GLS See Table 1

A4C LV TDI S0 Place sample volume (5 to 10 mm) at or within 1 cm of the insertion of the MVleaflets.

Angle of interrogation should be as parallel to Doppler beam as possible.Measure at end-expiration.Optimize scale and sweep speed (100 mm/s).Average both septum and lateral wall measurement.S0: Peak systolic velocity.

Modified A4CRV (2D)

RVD1 (� RVD2/RVD3)

RVD1: Basal RV diameter. Measured at the maximal transverse diameter in the basalone-third of the RV.

RVD2: Mid-RV diameter measured at the level of the LV papillary muscles.RVD3: RV length, from the plane of the tricuspid annulus to the RV apex.

CWD TV TR peak velocity(TRVmax)

Peak TR velocity is measured by CWD across the tricuspid valve. Ensure the CWD toflow angle is correctly aligned. Eccentric jets can lead to incomplete Dopplerenvelopes and underestimation of TR velocity. A high sweep speed (100 mm/s)can help to differentiate between true velocities and artifact. Measure from acomplete TR envelope. Choose the highest velocity. Accuracy is greatest whenultrasound and blood flow are parallel.

A4C RV (TDI) RV S0 PW tissue Doppler S0 wave measurement taken at the lateral tricuspid annulus insystole. It is important to ensure the basal RV free wall segment and the lateraltricuspid annulus are aligned with the Doppler cursor to avoid velocityunderestimation.

A disadvantage of this measure is that it assumes that the function of a singlesegment represents the function of the entire ventricle, which is not likely inconditions that include regionality such as RV infarction.

Normal value $9 cm/s (27).

Continued on the next page



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TABLE 2 Continued


A4C LateralTVannulus(MM)

TAPSE This is an angle-dependent measurement, and therefore, it is important to align theM-Mode cursor along the direction of the lateral tricuspid or mitral annulus.Select a fast sweep speed.

Measure total excursion of the tricuspid annulus.Normal value $17 mm (60).

2D ¼ 2 dimensional; BSA¼ body surface area; CWD ¼ continuous-wave Doppler; LA ¼ left atrium; LV ¼ left ventricle; MM ¼M-mode; MV ¼mitral valve; PW ¼ pulsed wave; RV ¼ right ventricle; RVD ¼ rightventricular diameter; TAPSE ¼ tricuspid annular plane systolic excursion; TDI ¼ tissue Doppler imaging; TR ¼ tricuspid regurgitation; TV ¼ tricuspid valve; other abbreviations as in Table 1.


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ventricular (RV) size and systolic function assess-ment, tricuspid regurgitant velocity (TRV), and bloodpressure measurement (Table 2). Measurement tech-niques are described in Tables 1 and 2, and the overallclinical approach to echocardiographic monitoring isdescribed in the Central Illustration.

BASELINE AND SERIAL ECHOCARDIOGRAPHIC

ASSESSMENT. The role of transthoracic echocardi-ography screening in the cardio-oncology setting is toassess cardiac function at baseline and to diagnoseCTRCD at the earliest possible stage (CentralIllustration). This enables informed decisionsregarding timely commencement of cardioprotectivemedications and the safe continuation of cardiotoxiccancer therapy. It is crucial that accurate and repro-ducible parameters of LV systolic function are used sothat a detected decline in LV systolic function trulyreflects toxicity (13).

Baseline risk stratification of cardiotoxicity musttake into consideration both the proposed cancertherapy and individual patient-related factors(Table 3). A more personalized tailored approach tosurveillance is recommended in increased-risk pa-tients compared with low-risk patients (CentralIllustration). Recent Heart Failure Association–International Cardio-oncology Society expert posi-tion statements add to the published reportsregarding the frequency of surveillance echocardio-grams in patients stratified to low, medium, or highrisk who then receive anthracyclines or trastuzumab(Table 4) (14,15). In patients with normal LV systolicfunction at baseline, subsequent echocardiograms inasymptomatic patients should be targeted studies(Table 2). However, any patient with new cardiovas-cular symptoms while receiving cancer therapyshould undergo a full echocardiogram (16).

The optimum frequency of echocardiograms dur-ing and after cancer therapy is unclear especially in

the context of current pandemics (e.g., COVID-19)(17,18). Recommendations for echocardiography dur-ing and after anthracycline-containing chemotherapyalso differ, with the majority of guidelines not quan-tifying frequency of monitoring (19,20). There is widevariation in guideline recommendations (19) on thefrequency of echocardiographic monitoring for pa-tients receiving trastuzumab, ranging from every3 months (21) to an undefined “periodically” (10)(Table 4). Furthermore, there is no strong evidence tosupport a specific schedule of screening or any evi-dence that it improves outcomes for screened pa-tients (22). However, screening every 3 months is stillrecommended by the U.S. Food and Drug Adminis-tration, although the frequency is admittedlycontroversial, and compliance is limited (23).

Historically, trastuzumab has been temporarilyheld or even discontinued in patients who develop LVsystolic dysfunction. However, there are increasingdata to suggest that patients with asymptomatic re-ductions in LVEF to 40% to 49%, with guidance froma cardio-oncology team and personalized monitoringand treatment, can safely complete their cancertreatment without a significant increase in cardiacevents (24,25). We therefore recommend a personal-ized approach to patient surveillance, as emphasizedin a position statement from the Heart FailureAssociation–European Association of CardiovascularImaging (15).

Echocardiography 3 to 12 months post-cardiotoxictreatment is recommended in all patients, with theoptimum timing dependent upon the individual pa-tient’s risk (16). Appropriate frequency of repeatechocardiography thereafter remains to be fullydefined and depends upon whether any cardiotox-icity occurred during the treatment phase (15), withinternational recommendations varying from 1- to5-year intervals (16,26). Decisions regarding long-

CENTRAL ILLUSTRATION Echocardiography Protocol in Patients Undergoing Treatment WithAnthracyclines/HER2-Positive–Targeted Therapy

Dobson, R. et al. J Am Coll Cardiol CardioOnc. 2021;3(1):1–16.

Assessment at baseline, during therapy (including patients on indefinite HER2-positive–targeted therapy in case of metastatic disease) and

long-term follow-up after the completion of cancer therapy. BSE ¼ British Society of Echocardiography; GLS ¼ global longitudinal strain;

LV ¼ left ventricular; LVEF ¼ left ventricular ejection fraction.



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TABLE 3 Identification of the Patient at Increased Risk of Cardiotoxicity

Lower Risk Increased Risk

Therapy-related risk factors

Lower lifetime dose of anthracycline<Doxorubicin 250 mg/m2 or equivalentNo previous anthracycline/trastuzumab-related cardiotoxicityAbsence of sequential anthracycline and trastuzumab therapyLow-dose radiation therapy to central chest including heart in radiation field <30 Gy

Increased lifetime dose of anthracycline>Doxorubicin 250 mg/m2 or equivalent—high risk>400 mg/m2 or equivalent—very high riskPrior anthracycline/trastuzumab-related cardiotoxicitySequential anthracycline and trastuzumab therapyHigh-dose radiation therapy to central chest including heart in radiation

field $30 Gy

Patient-related risk factors

MaleAge <50 yrsAbsence of traditional cardiovascular risk factors: Hypertension, smoking, obesity,

dyslipidemia, insulin resistancePast medical history:

Normal baseline LVEFAbsence of pre-existing cardiovascular disease (e.g., CAD, PAD, cardiomyopathy,

severe valvular heart disease, heart failure, or diabetes)Normal kidney function or chronic kidney disease stage 1

Biomarkers:Normal baseline troponin and/or NT-proBNPNormal cardiac troponin or NT-proBNP during cancer therapy

FemaleAge 50 to 64 yrs—high risk and $65 yrs—highest riskPresence of traditional cardiovascular risk factors: Hypertension, smoking,

obesity, dyslipidemia, insulin resistancePast medical history:

Reduced or low-normal LVEF (50% to 54%) pre-treatmentPresence of pre-existing cardiovascular disease (e.g., CAD, PAD,

cardiomyopathy, severe valvular heart disease, heart failure, or diabetes)Chronic kidney disease stage 2 (eGFR <78 ml/min/1.73 m2) (84)

Biomarkers:Elevated* baseline troponin and/or NT-proBNPElevated* cardiac troponin or NT-proBNP during cancer therapy

*Elevated above the upper limit of normal for local laboratory reference range.

CAD ¼ coronary artery disease; eGFR ¼ estimated glomerular filtration rate; LVEF ¼ left ventricular ejection fraction; NT-proBNP ¼ N-terminal pro–B-type natriuretic peptide; PAD ¼ peripheral arterialdisease.


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term surveillance should take into consideration apatient’s total anthracycline dose, exposure to otherpotentially cardiotoxic treatments (including radio-therapy), cardiovascular comorbidities, cardiotoxicityduring treatment, and LV systolic function duringand at the end of treatment.

ECHOCARDIOGRAPHY-BASED DEFINITIONS

OF CARDIOTOXICITY

The definition of cardiotoxicity is varied and notlimited to LV systolic dysfunction and CTRCD (19).The definition of cardiotoxicity based solely on LVEFalso varies significantly (10,16,21). We define CTRCDas a decrease in LVEF by >10% (10 absolute percent-age points) to a value <50%. This is in keeping withBSE-published normal/borderline normal ranges (27)and European Society for Medical Oncologyconsensus recommendations (26). A LVEF of 50% to54% is considered to be borderline low and willrequire more information before labelling the patientas having normal or abnormal LV systolic function.

We recommend that, if possible, 3D LVEF ismeasured due to both its reported superior repro-ducibility compared with 2D LVEF in patients un-dergoing anticancer therapy (28) and suggestions that3D LVEF changes are more pronounced than andprecede 2D LVEF changes in such patients (29). 3DLVEF has been shown to allow accurate serial quan-tification of LV systolic function and identification ofchanges in oncology patients (13). Declines in LVEFare usually accompanied by a significant change in

GLS. Therefore, if GLS is normal in the presence of areduced LVEF, a review of the echocardiograms toreassess the accuracy of all measurements is recom-mended. If there is still a significant and unexplaineddiscrepancy between change in LVEF and GLS, adju-dication with cardiac magnetic resonance (CMR) im-aging should be considered.

Normal GLS values vary with age, sex, loadingconditions, and different vendors; therefore, defini-tion of abnormal GLS is not straightforward. It isimportant that heart rate and blood pressure arerecorded because variation will need to be consideredif there are temporal changes in GLS measurements.Much of the existing published reports on GLS valuesare based on General Electric vendor-specific data,and for the purpose of this guideline, we define anormal GLS value as being �17% or more negative formales and �18% or more negative for females (30–32).A relative change in sequential GLS >15% (e.g., �22%to �18%) is considered to be significant (33). A wors-ening in GLS is known to predict a subsequent declinein LVEF, with GLS-guided cardioprotective therapypotentially reducing a decline in LVEF (34). Thechange in GLS is essential in recognition of car-diotoxicity, such that each patient acts as their owncontrol. For this reason, comprehensive baselineechocardiography before cancer therapy is critical.

Reduction in GLS into the abnormal range asdescribed or borderline values and declines in LVEFwithin the normal range should not be taken inisolation, especially in asymptomatic patients, butbe interpreted in the overall clinical context. A

TABLE 4 Frequency of Echocardiographic Monitoring During Anthracycline or Trastuzumab (Anti-HER2) Therapy According to

Published Guidelines

Guideline, Year (Ref. #) Recommendation for Frequency of Echocardiography During Therapy

HFA-EACVI, 2020 (15)

Anthracyclines Low risk*; after cycle of cumulative dose 240 mg/m2 doxorubicin or equivalent, then every additional 100 mg/m2 or every 2 cycles

Medium risk*; following 50% of planned total treatment and after cycle of cumulative dose 240 mg/m2 doxorubicin or equivalent

High risk*; every 2 cycles, consider after every cycle above 240 mg/m2 doxorubicin or equivalent

Anti-HER2 (neoadjuvant andadjuvant)

Low risk*; every 4 cycles (12 weeks)

Medium risk*; every 3 cycles (9 weeks), then reduce to every 4 cycles if stable at 4 months

High risk*; every 2 cycles 6 weeks), then reduce to every 3 cycles if stable at 4 months

Anti-HER2 (long term) Low risk*; every 4 cycles in year 1, every 6 cycles in year 2, then reduce to every 6 months

Medium risk*; every 3 cycles, then if stable reduce to every 6 months

High risk*; every 2 or 3 cycles for 3 months, then reduce to every 4 cycles in year 1, then reduce frequency

ESMO, 2020 (26)

Anthracyclines After a cumulative dose of 250 mg/m2 doxorubicin or equivalent, then after each additional 100 mg/m2

Anti-HER2 Every 3 months (higher-risk patients may require more frequent monitoring)

Anti-HER2 (long term) General surveillance, which may include cardiac imaging

ASCO, 2017 (16)

Anthracyclines Frequency of surveillance should be determined by health care providers. Routine surveillance imaging may be offered in patients consideredto be at increased risk of cardiac dysfunction.

Anti-HER2 Frequency of surveillance should be determined by health care providers. Routine surveillance imaging may be offered in patients consideredto be at increased risk of cardiac dysfunction.

CCS, 2016 (85)

Anthracyclines No recommendation made

Anti-HER2 Every 3 months

ESC, 2016 (10)

Anthracyclines After 200 mg/m2 of doxorubicin or equivalent

Anti-HER2 Every 4 cycles

ASE, 2014 (33)

Anthracyclines After 240 mg/m2 of doxorubicin or equivalent, then after each additional 50 mg/m2

Anti-HER2 Every 3 months

*Risk is calculated according to therapy and patient-related factors, including age, and cardiovascular risk factors. For more details, the reader is directed to the original guideline (15).

ASCO ¼ American Society of Clinical Oncology; ASE ¼ American Society of Echocardiography; CCS ¼ Canadian Cardiovascular Society; EACVI ¼ European Association of Cardiovascular Imaging;ESC ¼ European Society of Cardiology; ESMO ¼ European Society of Medical Oncology; HER ¼ human epidermal growth factor; HFA ¼ Heart Failure Association.



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decline in LVEF by >10 percentage points to an ab-solute value >50% with a lower limit of normal ofGLS is a grey area that might suggest potential sub-clinical cardiotoxicity, although in some cases, itmay reflect normal, physiological variability (35). Inthese circumstances, it is important to take otherfactors (such as symptoms, other echocardiographicparameters of LV systolic function, and biomarkers)into consideration. GLS may have added value,particularly in cases of borderline LVEF, with anormal strain measurement providing some reas-surance (36,37). Patients with normal LVEF, butabnormally low strain, also require further investi-gation to rule out potential causes such as cardiacamyloidosis, infiltration or hypertensive cardiomy-opathy (38). These echocardiograms should bereviewed (to also ensure adequate technical quality)in conjunction with a clinical assessment andbiomarker measurement. Certainly, there is a needfor longer-term data to define the natural history of

LVEF and GLS changes, as well as the prognosticimplications of potential subclinical cardiotoxicity.

RECOMMENDATIONS

Definition of cardiotoxicity by echocardiography:

� LVEF: A decline in LVEF by >10 absolute percent-age points to a value <50%,

Definition of probable subclinical cardiotoxicity byechocardiography:

� LVEF: A decline in LVEF by >10 absolute percent-age points to a value $50% with an accompanyingfall in GLS >15% (where GLS measurement isavailable).

Definition of possible subclinical cardiotoxicity byechocardiography:

� LVEF: A decline in LVEF by <10 absolute percent-age points to a value <50%.


9

or

� LV GLS: A relative percentage reduction in GLS by>15% from the baseline value.

The detection of cardiotoxicity or probable/possible subclinical cardiotoxicity is achieved viaadvanced echocardiographic measures (2D/3D LVEFand GLS). For best practice, centers undertakingsurveillance of these patients should have the abilityto perform 2D/3D LVEF and GLS assessment.

LV FUNCTION ASSESSMENT BY

ECHOCARDIOGRAPHY

CARDIAC RHYTHM AND RATE. Sequential assess-ments for those not in sinus rhythm may be prob-lematic. In atrial fibrillation due to the persistentvariation in cardiac cycle length, measures of ven-tricular systolic and diastolic function may havelimited reliability. When preceding and pre-precedingRR intervals are within 60 ms of each other and bothexceed 500 ms, measures of systolic function on asingle beat are similar to those averaged over 15 cy-cles of varying durations (39). These findings suggestthat selection of beats with similar RR intervals ismore important for reproducibility than the totalnumber of measurements made.

BLOOD PRESSURE. Recording of blood pressure isessential because parameters such as LVEF, tissueDoppler indices, and GLS are load dependent. Asubstantial increment of blood pressure may beresponsible for an apparent change in function,without necessarily indicating myocardial disease,because poorly controlled hypertension is associatedwith abnormal strain (40).ACCURATE ASSESSMENT OF 2D LVEF. LVEF is oneof the most commonly used echocardiographicmethods to assess LV systolic function. This repre-sents the fraction of blood within the LV that isejected in 1 cardiac cycle. Because it is difficult toquantify a 3D structure using 2D imaging, the tech-niques developed with 2D echocardiography rely onmeasuring the ventricle in standard planes.

We do not support the use of qualitative “eyeball”assessments to determine LVEF values or ranges. The2D volumetric Simpson’s method for the assessmentof LVEF is based on the principle of slicing the LVfrom the apex down to the mitral valve (MV) into aseries of discs. The volume of each disc is thencalculated using the diameter and thickness of eachslice. It is assumed that the LV is circular at eachlevel. Accuracy is improved by using diameters in 2planes, separated by 60� of rotation (apical 4 and 2chamber) so that the disc surface area is more

precisely defined. Acquisitions should be made atend-respiration, and the image should be adjustedusing gain, compress, and dynamic range to ensureoptimal endocardial delineation and elongation of theentire LV length, without foreshortening. High-quality images are critical for accurate quantifica-tion. For more detailed guidance, the reader isdirected to the BSE minimum dataset (SupplementalAppendix) (3). The endocardial surface should betraced at end-diastole and end-systole to encompassthe whole of the LV. Papillary muscles and trabecu-lations are excluded from the endocardial tracing andare considered part of the chamber. This can be ach-ieved either on the machine or by using an off-lineanalysis software package. LVEF is calculated as thedifference between end-diastolic volume and end-systolic volume (stroke volume) as a percentage ofthe end-diastolic volume. Intraobserver and interob-server variability has been reported as 3.3% and 4%respectively with a minimum detectable difference of9% to 11% (13,41). When describing 2D LVEF, thereport conclusion should always note the most recentestimate of LVEF and include a comparison with thebaseline value.3D LVEF. The 2D echocardiographic assessment ofLVEF has inherent limitations because it makes geo-metric assumptions of the LV. This consideration isespecially important for serial echocardiogramsbecause exact plane duplication is almost impossible.3D echocardiography, although still requiring high-quality, reproducible images, is an advance on theSimpson’s method because it allows contouring of thecavity within the 3D space of the echocardiographicvolume acquisition. Therefore, there is no assump-tion that the short-axis view of the ventricle is cir-cular. Instead, one can contour the actual shape of theventricle in all dimensions. Consequently, 3D LVEFcalculation has a smaller detected % change ofapproximately 5% to 8% and, because it is semi-automated, has better intra- and interobserver vari-ability (13). There is superior temporal variation of 3DLVEF compared with 2D LVEF over a 12-month periodin stable patients receiving chemotherapy (3% vs. 5%)(13). Commercially available scanners contain soft-ware tools that allow the 3D assessment of LV vol-umes and LVEF. It is to be remembered, however,that 3D imaging remains sensitive to image quality,and it is good practice to record and analyze both 2Dand 3D images, because deterioration of image qual-ity during follow-up is most likely to affect 3D images.There remains some variation in 3D LVEF calculationbetween specific vendors, and we recommend thatthe same machine and analysis software are used forserial echocardiograms (42). When reporting 3D LVEF





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findings, the conclusion should always note the mostrecent estimate of LVEF and include a comparison tothe baseline value.

Full-volume datasets allow the generation of a 3Ddataset with the final image of the heart created byacquiring several single or several subvolumes overthe corresponding number of sequential cardiac cy-cles. Attention to breath-hold is essential to avoidstitching artifact. The greater the number of sub-volumes used, the higher the frame rate and tem-poral resolution, albeit at greater risk of stitchingartifact. Newer technology allows increased volumerates and reduced time for complete cardiac volumeacquisition in the estimation of 3D LVEF, making itcomparable to CMR imaging (43). It should berecognized that there is a tradeoff between temporaland spatial resolution. Temporal resolution (i.e.,volume or frame rate) allows localization of ananatomic structure in a point in time. This can beimproved by reducing the sector size (width anddepth). Spatial resolution is the ability to differen-tiate 2 points in space and is dependent on thenumber of scan lines per volume (scan line density),However, increasing scan lines lengthens the acqui-sition time and lowers the volume rate (44).

Images should be obtained during shallow breath-ing, preferably in end-expiration. If deep inspirationis needed to obtain optimal image quality, this shouldbe documented in the echocardiogram report so thatit can be reproduced at the next visit. Finally, it isgood practice for the sonographer to quantify LVEFon 2D and 3D images while the patient is still present.Performing the analysis at the time also allows repeatimage acquisition in case of contouring difficulty.

How to acquire 3D echo volumes for LVEFassessment:

� Ensure high-quality electrocardiogram (ECG) tracewith a clear R-wave. This enables appropriate 3Dfull-volume triggering.

� Ensure the region of interest (ROI) is within the 3Dvolume sector. Reduce the sector as needed tofocus on the ROI.

� As for 2D imaging, adjust scanner settings so thatthe best 3D resolution is available.

� Adjust gain appropriately. Low gain settings resultin echo “dropout,” and excess gain reduces reso-lution and causes a loss of the 3D perspective ordepth in the dataset.

� Optimize frame rate and adjust number of sub-volumes according to patient breath-holding ca-pacity as needed.

� Acquire images with the probe maintained in asteady position and at end-expiration.

� Following acquisition, review the image to look forany stitch artefact.

CONTRAST ECHOCARDIOGRAPHY/ULTRASOUND

ENHANCING AGENTS. Inadequate LV endocardialborder definition can lead to errors in LV volume andLVEF estimation. Accurate LVEF assessment isparticularly important where values obtained fall onboundaries that influence treatment decisions. Poorendocardial definition can occur in patients under-going cancer treatment (e.g., following mastectomy,chest irradiation, or breast reconstruction surgery)(33) or secondary to body habitus. The use of echo-cardiographic contrast for LV chamber opacification isnow widely accepted when 2 contiguous LV segmentsfrom any apical view are not adequately visualized onnoncontrast images (45). Tracing LV borders morereliably leads to inclusion of LV trabeculation withinthe LV cavity after contrast. As a result, LV volumes(both in systole and diastole) are commonly greaterthan those recorded with noncontrast imaging,although LVEF is usually analogous. The minimumdetectable difference for 2D contrast LVEF has beennoted to be in the order of 4% (46), which is signifi-cantly better than the 9% to 11% for noncontrast 2DLVEF. However, the superior performance of LVcontrast has not been consistently proven. One studydemonstrated inferior reproducibility with contrastechocardiograms compared with noncontrast 2D and3D echocardiograms (13). Use of the same methodol-ogy in sequential testing is thus recommended. It is tobe noted that the use of contrast has unpredictableeffects on 2D speckle tracking and is best done afterstrain acquisition.

TISSUE DOPPLER ASSESSMENT OF SYSTOLIC AND

DIASTOLIC FUNCTION. Tissue Doppler echocardiog-raphy has become an established component of thediagnostic ultrasound examination, enhancing inter-rogation of myocardial motion. Although LVEF re-flects the sum contribution of several regions, it doesnot provide information on regional function or onthe underlying myocardial mechanical activity. Con-ventional Doppler techniques assess velocity of bloodflow by measuring high-frequency, low-amplitudesignals from small, fast-moving blood cells. TissueDoppler imaging (TDI) uses the same Doppler princi-ples to quantify the higher-amplitude, lower-velocitysignals of myocardial tissue motion. TDI depictsmyocardial motion at a specific location in the heart.High-velocity signals from the blood are filtered outand amplification scales suitably adjusted so thatDoppler signals from tissue motion can be recorded.Tissue velocity indicates the rate at which a particularpoint in the myocardium moves toward or away from


11

the transducer. The accuracy of TDI is angle depen-dent and only measures the vector of motion that isparallel to the direction of the ultrasound beam. Meanmitral annular S0 should be acquired at end-expiration. For more detailed guidance, the reader isdirected to the BSE minimum dataset (SupplementalAppendix) (3). Normal age-related values for meanmitral annular S0 are described in recent guidance(27). Both tissue Doppler and grey scale imaging havebeen used to calculate mitral annular planedisplacement, which is a longitudinal functionparameter analogous to strain.

In breast cancer patients receiving anthracyclineswith or without trastuzumab, diastolic dysfunctionhas been reported to precede systolic dysfunction andCTRCD (47). We recommend diastolic assessmentshould be undertaken in all baseline echocardio-grams. Along with mitral E and A maximum velocity(Vmax), E/A ratio, left atrial volumes, and TRV, TDI isa key part of the assessment of diastolic function (48).For more details on the grading of diastolic function,the reader is directed to the current American Societyof Echocardiography/European Association of Car-diovascular Imaging guidelines on the assessment ofdiastolic dysfunction (49).

SPECKLE TRACKING

ECHOCARDIOGRAPHY: GLS

The term strain refers to an object’s fractional or per-centage change from its original, unstressed dimen-sion and reflects the deformation of a structure. Whenapplied to myocardium, this deformation or straindirectly describes the contraction/relaxation pattern.At rest, an object that has an initial length (L0) can bestretched or compressed to a new length (L). Thischange in length is usually represented as a percent-age, with a negative score indicating a shortening inlength. Should L equal L0, then strain remains zero.

Although LVEF is simple and intuitive, and sup-ported by prognostic information, it has importantlimitations including image quality dependence, geo-metric assumptions, and insensitivity to early disease(which is characterized by disturbances of longitudi-nal function). Strain measurements, like LVEF mea-surements, are dependent on endocardial bordertracing and therefore also rely on image quality.

The myocardial fiber orientation of the LV is com-plex. The major limitation of the Doppler-basedapproach is the angle dependency required duringimage acquisition (50,51). This has been overcome byspeckle tracking echocardiography, which is based ontracking the pattern of speckles generated by reflectedultrasound signal. Different regions of myocardium

have a unique speckle pattern that moves from oneframe to the next. Dedicated speckle tracking softwareenables this movement to be quantified via severalparameters (such as longitudinal strain).

GLS is measured using a combination of the apical 2-chamber (A2C), 3-chamber (A3C), and 4-chamber(A4C) views (52). Longitudinal strain is the degree ofdeformation from base to apex. During systole,contraction in this plane leads to fiber shortening,represented as a negative percentage value (i.e., themore negative the value, the greater the deformation).Although global circumferential and radial strain mayalso indicate cardiotoxicity, there are less data tosupport their clinical use (35), hence, the focus on GLS.GLS has been shown to be superior to 2D LVEF withregard to reproducibility in patients receiving trastu-zumab (53) and has been suggested that it is morereproducible with appropriate echocardiographictraining (54). It is therefore best practice that cardio-oncology echocardiograms are performed on ma-chines able to calculate GLS and which have 3D capa-bilities. Small, but statistically significant, differencesbetween vendors exist; therefore the same acquisitionplatform and analysis software should be used for se-rial echocardiograms (55–57). The ability to performGLS and 3D measurements is beyond the current BSEpersonal accreditation standards. It is thereforeimportant that individuals undertaking cardio-oncology echocardiograms are suitably trained inacquisition and analysis of these advanced echocar-diography measures in a reproducible and consistentmanner. In addition, echo departments should estab-lish and reassess their intra- and interobserver vari-ability of 2D LVEF, 3D LVEF, and GLS.

How to perform GLS:

� GLS is calculated using the standard A3C, A4C, andA2C views.

� Ensure an optimal ECG signal with minimal heartrate variability is present across 3 cardiac cycles.

� Maintain a frame rate of 40 to 90 frames/s (33) at anormal heart rate.

� Focus on the LV with appropriate adjustment ofwidth and depth.

� The technique used to select the appropriate ROI isvendor-specific, and the reader is advised to con-sult individual machine/software technical guide-lines for further guidance. For General Electricmachines/software, adjust the overlay for the ROI.In the A4C view, the ROI begins at the septal MVannulus, progresses to the apex, and ends at thelateral MV annulus. In the A2C view, the ROI startsat the inferior MV annulus and extends through tothe apex and then to the anterior wall MV annulus.



TABLE 5 Key Echocardiographic Recommendations for Best Practice

Baseline assessment Full BSE minimum dataset echocardiogram, vital signs, and GLS/3D volumes (Table 1)

Follow-up assessment Targeted echocardiogram (Table 2)

If new symptoms, then full echocardiogram as per baseline assessment

Definition of cardiotoxicity LVEF: a decrease in LVEF by >10 absolute percentage points to a value <50%

Definition of probable cardiotoxicity by echocardiography LVEF: decrease in LVEF by >10 absolute percentage points to a value $50% with anaccompanying fall in GLS >15% (where GLS measurement available)

Definition of possible cardiotoxicity by echocardiography LVEF: a decrease in LVEF by <10 absolute percentage points to a value <50% or LV GLS:when LVEF $50%, a relative percentage reduction in GLS by >15%

Poor endocardial definition Consider contrast echocardiography when endocardial definition precludes the accurateassessment of LVEF (e.g., when a minimum of 2 contiguous LV segments from anyapical view are not seen on noncontrast images)

Depending on local expertise and availability, CMR imaging is an alternative modality in this context

CMR ¼ cardiac magnetic resonance; other abbreviations as in Tables 1 to 3.



12

In the A3C view, the ROI starts at the posterior wallMV annulus, extends to the apex and finally to thebase of the septal wall, taking care not to extendinto the LV outflow tract.

� Two contours for speckle tracking are visible andshould be aligned with the relevant area ofinterest:B The endocardial border—the inner contour of

the myocardiumB The epicardial border—the outer border of the

myocardium (be careful to exclude the pericar-dium, especially if automated analysis softwareis used. Inclusion of pericardium will lead to anunderestimation of strain)

� Use optimal gain settings and breath-hold tech-niques to clearly delineate the endocardial andepicardial borders.

� During post-processing, the ROI should be alignedas accurately as possible to reflect the 17-segmentLV model.

RIGHT HEART ASSESSMENT. Right heart (RH) struc-ture and function has not traditionally been incor-porated into the definition of CTRCD. However,there is increasing evidence that RH abnormalitiesmay be prognostically significant (58,59), andtherefore assessment of the RH should be obtainedto include RV dimensions, RV S0, tricuspid annularplane systolic excursion, and TRV. Abnormalities inRH structure and function on serial echocardiogra-phy should be discussed with a cardio-oncologistand may require full assessment of the RH as perthe BSE practical guideline for RH assessment andthe BSE guideline on the assessment of pulmonaryhypertension (60,61).

ALTERNATIVE IMAGING MODALITIES

Although echocardiography remains the first-lineinvestigation for the detection of CTRCD, there is a

complementary role for other imaging modalities,particularly in patients with inadequate echocardio-graphic windows. Traditionally, multigated acquisi-tion scans have been used in the assessment of LVsystolic function however, the associated radiationexposure (a particular issue with the inevitable serialscans) and limited structural information availablemakes this an inferior investigation (62). CMR imag-ing may be required in patients with poor echocar-diographic windows or for tissue characterization(e.g., cardiac masses and cancer treatment–relatedmyocarditis). Low inter- and intrareader variabilitymake it the optimal technique for detecting smallchanges in LVEF in serial scans; however, its use isstill limited by its availability and cost (63,64). Therole of cardiac computed tomography is mainly in thenoninvasive evaluation of coronary artery disease,but it can also be used to assess pericardial diseaseand valvular heart disease, and in the imaging ofcardiac tumors (65,66).

RECOMMENDATION.

� Contrast 2D echocardiography should be consid-ered when subendocardial definition precludes theaccurate assessment of LVEF, that is, when aminimum of 2 contiguous LV segments from anyapical view are not seen on noncontrast images(45).

� Depending on local expertise and availability, CMRimaging is an alternative modality, particularly forpatients with poor echocardiographic windows.

� The same imaging modality should be used forsequential scans.

CLINICAL RISK STRATIFICATION FOR CARDIOTOXICITY.

Risk stratification for cardiac dysfunction is recom-mended before the commencement of potentiallycardiotoxic cancer treatment in all patients (14,16). Aclinical history and cardiovascular examination,including blood pressure measurement, should be


13

performed in order to aid assessment of risk (Table 3).All patients should also have a baseline 12-lead ECG.

Although outside the scope of this document, bio-markers (troponin and N-terminal pro–B-type natri-uretic peptide [NT-proBNP]) may be considered inhigh-risk patients to assist further risk stratification(Table 3). Biomarkers may be able to detect subclini-cal signs of LV systolic and diastolic dysfunctionbefore a decline in LVEF (67). Elevated baseline levelsshould prompt more frequent monitoring becausethere is some evidence that abnormal baseline high-sensitivity troponin is associated with an increasedrisk of developing complications with chemotherapy.There is also an association between troponin releaseafter high-dose chemotherapy and subsequent car-diac events (68–70). Persistent serial elevation of NT-proBNP is associated with an increased risk ofdeveloping overt heart failure, whereas a transientrise is not (71). However, discussion of the utility andprognostic value of biomarkers is beyond the scope ofthis guideline, and the reader is directed to additionalreferences (27,72).

Defining the high-risk patient is challenging.Although there is no validated unifying risk calculatorthat is applicable to all cancer types and therapies(73), recently published guidelines can help clinicianswith risk stratification (14). This highlights the needfor a tailored and individualized approach to theassessment, treatment, and monitoring of cardio-oncology patients.

REFERRAL TO A CARDIO-ONCOLOGY SERVICE

The cardio-oncology team is composed of specializedhealth care professionals who work together to pro-vide “consistent, continuous, coordinated and cost-effective care during the cancer process” (74). Thishighly specialized service is involved in patient care,cardio-oncology research, and regional co-ordinationof services (75).

Echocardiography is pivotal to decision-making incardio-oncology, for example, when to considerreferral to a cardio-oncologist, when to initiate car-dioprotective medications or heart failure therapy,and when to hold or discontinue cardiotoxic cancertherapy. Early detection of cardiac dysfunction, withprompt initiation of cardioprotective medications,increases the likelihood of LVEF recovery and mayreduce the cardiac event rate (76).

All patients with confirmed cardiotoxicity requirereferral to a cardio-oncology service. Any patient withpre-existing LV systolic dysfunction should be

discussed with the cardio-oncology team, ideallybefore the commencement of cardiotoxic cancertherapy (2). With increasing evidence that a signifi-cant reduction in GLS accurately predicts subsequentcardiotoxicity (35), referral to a cardio-oncology ser-vice for expert review could be considered in patientswith >15% reduction in GLS despite a normal LVEF.

TREATMENT THRESHOLDS. Patients who developCTRCD (symptomatic or asymptomatic) benefit fromearly introduction of angiotensin-converting enzymeinhibitors/angiotensin receptor blockers and/or beta-blockers (77). Treatment thresholds vary in the pub-lished reports (10,78,79). Treatment in asymptomaticpatients with declines in GLS, but not in LVEF, re-mains controversial (13,80). Closer monitoring and/orstarting cardioprotective treatments are options to beconsidered. There is no evidence at present to holdcancer therapy based upon abnormal strain mea-surements alone.

Recent studies have investigated the role of pre-treatment with cardioprotective medications in can-cer patients embarking on cardiotoxic therapy(81–83). Results have been mixed, and such strategiescannot currently be recommended as routinepractice.

CONCLUSIONS

Cardio-oncology is a relatively new and rapidlydeveloping subspecialty. Echocardiography is a keyimaging modality in the initial assessment and sub-sequent monitoring of patients treated withcommonly used cardiotoxic drugs such as anthracy-clines and trastuzumab. High-quality targeted LVEFassessment incorporating 3D volumetric analysis andstrain measurement can be used to safely monitorpatients during and after treatment. Key echocar-diographic recommendations are shown in Table 5.

FUNDING SUPPORT AND AUTHOR DISCLOSURES

This work was supported by National Institutes of Health grant R01

HL 118018 (Dr. Ky). The authors have reported that they have no re-

lationships relevant to the contents of this paper to disclose.

ADDRESS FOR CORRESPONDENCE: Dr. RebeccaDobson, Liverpool Heart & Chest Hospital, ThomasDrive, Liverpool L14 3PE, United Kingdom. E-mail:[email protected]. OR Dr. Arjun K.Ghosh, Barts Heart Centre, St. Bartholomew’s Hospi-tal, West Smithfield, London EC1A 7BE, UnitedKingdom. E-mail: [email protected]. Twitter:@theharveys, @arjunkg, @DrDanAugustine.

mailto:[email protected]

mailto:[email protected]

https://twitter.com/theharveys

https://twitter.com/arjunkg

https://twitter.com/DrDanAugustine



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KEY WORDS anthracycline,echocardiography, guidelines, HER2 therapy,imaging

APPENDIX For the full British Society ofEchocardiography minimum transthoracicdataset, please see the online version of thispaper.





































Minerva Access is the Institutional Repository of The University of Melbourne

Author/s:

Dobson, R; Ghosh, AK; Ky, B; Marwick, T; Stout, M; Harkness, A; Steeds, R; Robinson, S;

Oxborough, D; Adlam, D; Stanway, S; Rana, B; Ingram, T; Ring, L; Rosen, S; Plummer, C;

Manisty, C; Harbinson, M; Sharma, V; Pearce, K; Lyon, AR; Augustine, DX; British Society of

Echocardiography (BSE) and theBritish Society of Cardio-Oncology (BCOS),

Title:

BSE and BCOS Guideline for Transthoracic Echocardiographic Assessment of Adult Cancer

Patients Receiving Anthracyclines and/or Trastuzumab.

Date:

2021-03

Citation:

Dobson, R., Ghosh, A. K., Ky, B., Marwick, T., Stout, M., Harkness, A., Steeds, R., Robinson,

S., Oxborough, D., Adlam, D., Stanway, S., Rana, B., Ingram, T., Ring, L., Rosen, S.,

Plummer, C., Manisty, C., Harbinson, M., Sharma, V. ,... British Society of Echocardiography

(BSE) and theBritish Society of Cardio-Oncology (BCOS), (2021). BSE and BCOS Guideline

for Transthoracic Echocardiographic Assessment of Adult Cancer Patients Receiving

Anthracyclines and/or Trastuzumab.. JACC CardioOncol, 3 (1), pp.1-16.

https://doi.org/10.1016/j.jaccao.2021.01.011.

Persistent Link:

http://hdl.handle.net/11343/287156

File Description:

Published version

License:

CC BY-NC-ND

Documents

BSE and BCOS Guideline for Transthoracic Echocardiographic