Open access Heart failure and cardiomyopathies

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Update in imaging of cancer therapy-­
related cardiac toxicity in adults
Esmée C de Baat  ‍ ‍,1 Willeke R Naaktgeboren  ‍ ‍,2,3 Tim Leiner  ‍ ‍,4
Arco J Teske  ‍ ‍,5 Jesse Habets  ‍ ‍,4,6 Heynric B Grotenhuis  ‍ ‍7

►► Prepublication history and ABSTRACT dysfunction (cancer treatment-­ related

additional material is published Over the past decades, prognosis of patients with cancer cardiac dysfunction (CTRCD)) later in life.
online only. To view please visit
has strongly improved and the number of cancer survivors CTRCD may progress to heart failure over
the journal online (http://​dx.​doi.​
org/​10.​1136/​openhrt-​2020-​
is rapidly growing. Despite this success, cancer treatment time.2 The incidence and degree of CTRCD
001506). is associated with development of serious cardiovascular depends on type of the used cancer drug,
diseases including left ventricular (LV) systolic dysfunction, cumulative dose and (pre-­ )existing cardio-
To cite: de Baat EC, heart failure, valvular disease, myocardial infarction,
vascular comorbidities.3
Naaktgeboren WR, Leiner T, arrhythmias or pericardial diseases. Serial non-­invasive
Currently, echocardiographic imaging is
et al. Update in imaging of cardiac imaging is an important tool to detect early signs
cancer therapy-­related cardiac of cardiotoxicity, to allow for timely intervention and the method of choice for the evaluation of
toxicity in adults. Open Heart provide optimal circumstances for long-­term prognosis. myocardial function during and after cancer
2021;8:e001506. doi:10.1136/ Currently, echocardiographic imaging is the method of therapy. Left ventricular (LV) ejection frac-
openhrt-2020-001506 tion (EF) is frequently used as predictor for
choice for the evaluation of myocardial function during
and after cancer therapy. However, 2D echocardiography cardiac outcomes, but is not the optimal
JH and HBG contributed equally. may fail to detect subtle changes in myocardial function, parameter for detection of subtle alter-
potentially resulting in a significant delay of therapeutic ations in systolic myocardial performance.4
Received 5 November 2020 intervention to impede advanced cardiac disease states Compensatory mechanisms may mask subtle
Revised 8 January 2021 with more overt systolic dysfunction. Strain imaging is
Accepted 22 February 2021
LV dysfunction and clinical manifestations
a promising method for early detection of myocardial
of myocardial injury can therefore occur
dysfunction and may predict future changes in LV ejection
fraction. The use of three-­dimensional echocardiography
years after cancer therapy.4 Asymptomatic
may overcome the limitations of 2D echocardiography patients with CTRCD may remain unrec-
with more precise and reproducible measurements of ognised by serial LVEF assessment, so early
LV performance. Cardiac MRI is the gold standard for therapeutic intervention can be delayed until
volumetric assessment and can also be used to perform a later cardiac disease state. Early treatment
myocardial tissue characterisation. Visualisation of with heart failure medication may improve
oedema and fibrosis may provide insights into the degree recovery of myocardial dysfunction in a
and disease course of cardiotoxicity and underlying substantial part of patients.5
pathophysiological mechanisms. There is growing body of In recent years, the field of cardio-­oncology
literature regarding the promising role of these advanced has substantially evolved and the number of
imaging modalities in early detection of cardiotoxicity.
published studies is growing exponentially.
With this overview paper, new insights and recent results
in literature regarding echocardiographic and cardiac
Accordingly, the purpose of this overview
magnetic resonance imaging of cancer therapy-­related paper is to provide a summary of the latest
cardiac dysfunction in post-­cancer therapy adults will be insights and recent results in literature about
highlighted. the current role of echocardiographic and
cardiac magnetic resonance imaging (MRI)
monitoring of CTRCD in adult patients with
cancer and survivors.
INTRODUCTION Hence, a non-­systematic literature search
© Author(s) (or their Over the past decades, prognosis of patients in PubMed and EMBASE was performed to
employer(s)) 2021. Re-­use with cancer has strongly improved and extract original reports about imaging param-
permitted under CC BY-­NC. No the number of cancer survivors is rapidly eters for cardiac surveillance in patients with
commercial re-­use. See rights
and permissions. Published growing.1 Despite this success, cancer treat- cancer treated with cardiotoxic treatment.
by BMJ. ment is associated with increased risk of A narrative synthesis of those reports with
For numbered affiliations see morbidity and mortality during long-­ term potential impact on clinical practice and
end of article. follow-­up.2 Current anticancer protocols future research is provided in the current
include anthracyclines, tyrosine kinase manuscript. Imaging modalities as equilib-
Correspondence to
Dr Heynric B Grotenhuis; ​H.​B.​
inhibitors and monoclonal antibody rium radionuclide angiography (also known
Grotenhuis@​umcutrecht.​nl therapy, which can cause ventricular systolic as multigated acquisition scan), cardiac CT

de Baat EC, et al. Open Heart 2021;8:e001506. doi:10.1136/openhrt-2020-001506   1

Open Heart

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and nuclear imaging are considered beyond the scope a relative percentage decrease of >15% when compared
of this article. with baseline. Changes of <8% are considered normal
as this concerns inter-­variability and intra-­variability of
measurements.4 A recent prospective study in adults with
ECHOCARDIOGRAPHY lymphoma or leukaemia who were treated with a cumula-
LV systolic function tive anthracyclines dose up to 300 mg/m2, demonstrated
The most widely used method for the evaluation of LV that (2D) GLS >−17.45% at a cumulative anthracycline
function in patients with cancer at risk for CTRCD is dose of >150 mg/m2 is an independent predictor of
assessment of LVEF by two-­dimensional (2D) echocardi- future CTRCD, defined as a decrease in the LVEF of
ography.4 The European Society of Cardiology position >10% points to a value <53%.12 Pretreatment measure-
paper from 2016 defined the lower limit of normal of ments of GLS in this cohort were significantly lower in
LVEF as 50%, whereas the American Society of Echocardi- the CTRCD group than in the non-­CTRCD group, which
ography (ASE)/European Association of Cardiovascular may suggest an increased baseline risk profile for cardio-
Imaging (EACVI) expert consensus from 2014 defined vascular disease. This finding is supported by the study of
CTRCD as a decrease in LVEF exceeding 10% points, to Ali et al; their results demonstrated that reduced baseline
a value <53%.2 4 However, LVEF measured by 2D echo- GLS was a strong predictor of cardiac events in patients
cardiography is less suited to detect subtle changes in with haematologic cancers. A GLS threshold of −17.5%
systolic function since the variability in LVEF measures before anthracycline therapy would have correctly identi-
can be approximately 10%.6 This may be caused by LV fied 86% of the patients who develop a cardiac event after
geometric assumptions and difficulties in visualising the start of chemotherapy, defined as symptomatic heart
apex. Abnormalities in regional wall displacement can failure or cardiac death.13
also be difficult to detect with 2D echocardiography.4 In In addition, worse basal longitudinal strain after
addition, LVEF is susceptible to volume loading condi- chemotherapy was—in contrast to worse GLS—associ-
tions which may vary significantly during chemotherapy. ated with CTRCD in 61 anthracycline-­treated patients.
Changes in LVEF ultimately occur when compensa- Since GLS is the average of all LV segments, it is possible
tory mechanisms fail in the affected myocardium. Recent to underestimate regional impairment, whereas basal
developments in echocardiographic techniques including longitudinal strain may be a more sensitive marker of
myocardial strain by speckle tracking echocardiography CTRCD. However, further research is needed to assess its
(STE) and three-­ dimensional (3D) echocardiography clinical relevance.14
offer possibilities for more accurate and subclinical Global circumferential strain (GCS) may also be
detection of systolic dysfunction.6 7 Thavendiranathan et predictive for the occurrence of CTRCD. In the study of
al demonstrated that during treatment of patients with Narayan et al, every 1% reduction in GCS compared with
breast cancer with stable cardiac function, estimations of baseline circumferential strain was associated with an OR
LVEF by 3D echocardiography had temporal variability of of 1.21 (95% CI 1.10 to 1.34) for developing CTRCD in
approximately 6%.6 women receiving breast cancer therapy (n=135), inde-
pendent of relevant co-­variables such as age, history of
Myocardial deformation cardiovascular risk factors, treatment regimen and time
STE quantifies myocardial deformation by tracking since start of treatment.15
speckle displacement during the cardiac cycle. Strain A novel deformation parameter—area strain (AS)—
is expressed as percentage, which corresponds with the can be obtained with 3D STE. This parameter is calcu-
amount of deformation in a region of interest (ie, short- lated by combining the effects of GLS and GCS, so AS can
ening or lengthening) in respect to the initial length, be considered as parameter that integrates LV myocar-
often measured at the end of diastole. The most eval- dial deformation.16 In 67 patients with breast cancer, the
uated STE parameter is 2D global longitudinal strain mean of global AS (%) deteriorated significantly between
(GLS), which is the average of the strain values in the baseline and after anthracycline therapy (−30.2±4.5 and
longitudinal direction of all 17 segments according to −27.5±5.4, respectively).17
the ASE/EACVI LV segmentation model.8 Recently, 3D
strain measurements are emerging, for which, similar Right ventricular (RV) function
to 3D LVEF assessment, no multiple apical images are Assessment of RV function is considered increasingly
required. important. A recent report in patients with cancer treated
In the last decade, landmark reports demonstrated the with cardiotoxic treatment demonstrated concomitant
additive value of strain assessment after cardiotoxic treat- abnormalities in longitudinal strain of the free RV wall
ments.9–11 These results revealed that early decreases in in 75% of cases (n=20) with LVEF drop >10% to <53%
deformation parameters during or after cancer therapy in (6 months after initiation of chemotherapy).18 Conven-
adults allowed to predict subsequent LVEF deterioration. tional RV functional parameters (ie, tricuspid annular
The ASE/EACVI Expert Consensus therefore strongly plane systolic excursion) were within normal ranges,
supports the use of GLS during follow-­up, with a clinically suggesting that this novel RV strain parameter could be
significant deterioration of LV deformation supported by useful as early marker for (sub)clinical RV toxicity. These

2 de Baat EC, et al. Open Heart 2021;8:e001506. doi:10.1136/openhrt-2020-001506

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results should be affirmed in larger studies with a longer LVEF can be the result of an increased left ventricular end
follow-­up period. systolic volume (LVESV) or reduction of left ventricular
end diastolic volume (LVEDV). CTRCD is associated
LV mass and diastolic function with an increased LVESV (with a preserved LVEDV)—as
Lipshultz et al demonstrated that both LV thickness– a reflection of reduced myocardial contractility—while
dimension ratio and LV mass were significantly reduced reduced LVEDV can, for example, be observed in patients
in anthracycline-­ treated childhood cancer survivors.19 who are volume-­depleted during chemotherapy.26 Two
However, in adults, early evidence of remodelling may recent studies demonstrated that CTRCD, based on
be reversible as Narayan et al demonstrated increased LV drop in strain or LVEF measurements, was related to an
mass 1 year after anthracycline therapy which normalised isolated decline in LVEDV in 16%–19% of patients, indi-
in the years thereafter.20 cating that in part of the patients with decreased systolic
Reduced LV diastolic function may also occur as part of function, this may be the result of volume depletion.27 30
CTRCD, as reflected by abnormal mitral E velocity, E/A Also important, an increased LVESV due to CTRCD can
ratio, isovolumic relaxation time or tissue Doppler veloci- (partly) be compensated by increased LVEDV as part
ties.4 Anthracycline dose, age at treatment and BMI have of cardiac remodelling, to preserve LVEF and cardiac
been reported as risk factors of diastolic dysfunction.21 22 output. Evaluation of LV dimensions by cardiac MRI
However, the prognostic value of LV diastolic impairment should therefore be an integral part of cardiac evalua-
to predict CTRCD is doubtful because of inconsistent tion, in addition to systolic function parameters.
results regarding its ability to predict subsequent occur- LV mass can also be measured by cardiac MRI with
rence of systolic dysfunction.20 22 23 higher accuracy and reproducibility compared with
echocardiography.31 Neilan et al demonstrated an inverse
CARDIAC MAGNETIC RESONANCE IMAGING correlation between decrease in LV mass after chemo-
Cardiac MRI is a non‐invasive imaging technique that therapy and anthracycline dose, and that LV mass index
allows for accurate and reproducible assessment of <57 g/m2 was a predictor of adverse cardiac events.32
biventricular volumes, mass and function with negligible Also, Jordan et al showed a significant association between
inter-­observer and intra-­observer variability.24 25 Besides worsening of heart failure symptoms and declines in LV
anatomical and functional assessment, cardiac MRI allows mass after accounting for both changes in LVEF and
for myocardial tissue characterisation by use of late gado- changes in body weight.33 This may suggest that remod-
linium enhancement (LGE) and quantitative mapping elling of the LV structure precedes myocardial function
techniques (T1 and T2 mapping).26 impairment. Evaluation and quantification of LV mass by
cardiac MRI is therefore advised in (suspected) CTRCD.
LV function
For the surveillance of oncology patients, cardiac MRI RV function
-derived LVEF is considered as reference standard for LV In addition, cardiac MRI can be used to study RV perfor-
systolic performance.2 24 To detect small changes in LVEF, mance. Several studies have demonstrated significant
assessment with cardiac MRI is well-­suited in patients with changes in RV systolic function, structure and dimensions
good health and non-­cancer heart failure with a temporal during and after systemic cancer treatment.34–36 Recently,
variability of 2.4%–7.3%.25 a prospective study of patients with breast cancer (n=41)
Recent reports have demonstrated that also cardiac demonstrated a significant decrease in RVEF from 58.3%
MRI-­derived LV strain allows detecting subclinical LV (95% CI 57.1% to 59.5%) to 53.9% (95% CI 52.5% to
dysfunction, during and after potentially cardiotoxic 55.4%, p<0.001) and increases in right ventricular end
cancer therapy.27 28 During follow-­up of 41 trastuzumab-­ diastolic volume (RVEDV) and right ventricular end
treated patients, significant reductions in GLS and GCS systolic volume (RVESV) at 6 months after initiation of
were observed at 6 and 12 months when compared with trastuzumab, however, these measurements reversed after
baseline. These alterations were related with concurrent completion of therapy. RVEF and LVEF changed in a
decreases in LVEF.29 To enhance the potential transition similar pattern, but the relationship was non-­significant.36
from echocardiographic LV-­ measurements to cardiac Further studies are required to explore the prognostic
MRI, Jolly et al proposed an automated measurement value of RV evaluation in oncology patients.
of GCS from CMR cine images in patients treated with
chemotherapy. They demonstrated that GCS can be Myocardial tissue characterisation
obtained in ~7 min from routine cine LV short axis images Imaging by cardiac MRI enables visualisation and
in 98.6% of the patients (n=72) and the observed wors- characterisation of myocardial tissue. 37 38 Formation
ening in GCS correlated with LVEF decline on cardiac of fibrosis due to collagen breakdown is one of the
MRI.28 proposed molecular mechanisms of anthracycline-­
associated myocardial remodelling. 39 There are several
LV volume cardiac MRI techniques to detect fibrosis, including
Alterations in LV dimensions should always be consid- LGE imaging and mapping parameters. Visualisation
ered when evaluating changes in LVEF, since a decline in of fibrosis with LGE is generally a result of regional

de Baat EC, et al. Open Heart 2021;8:e001506. doi:10.1136/openhrt-2020-001506 3

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differences in signal intensity.37 Since interstitial the difficulty of interpreting mapping measurements
fibrosis as late effect of cancer treatment is likely to be in individual patients.44
diffuse, 24 LGE seems less suitable for the surveillance A landmark study of Jordan et al compared pretreat-
of CTRCD,35–37 40–42 except for the detection of toxic ment (n=37) and post-­t reatment patients with cancer
myocarditis or previous cardiac events such as myocar- (n=37) with cancer-­ f ree controls (n=236), demon-
dial infarcts.40 To detect diffuse myocardial diseases, strating elevated ECV 3 years after anthracycline treat-
specific mapping parameters (T1, T2, T2*) and extra- ment.45 It is important to stress that cardiovascular
cellular volume (ECV) are important cardiac MRI risk factors, often present in patients with cancer,46
techniques that depend on molecular environment in are associated with elevations in ECV. Increase in
a myocardial voxel and quantify intracellular changes ECV in this study was independent of cardiovascular
of the cardiomyocyte and extracellular changes in the risk factors, which corroborates the hypothesis that
myocardial interstitium.37 38 myocardial fibrosis develops after cancer treatment.45
Molecular environment changes may be caused by Accordingly, pretreatment cardiac MRI is crucial
oedema, interstitial fibrosis or other more rare causes to interpret the myocardial tissue characteristics
(ie, cardiac amyloidosis). Increases in T1 and T2 reflected by cardiac MRI. A more recent study indi-
values reflect myocardial fibrosis and oedema, respec- cated that interstitial myocardial fibrosis—reflected
tively. As a result of these processes, the extracellular by elevated ECV—may arise within 3 months after
matrix can expand, expressed by an increased ECV.38 initiation of cardiotoxic chemotherapy (71% received
In a recent pig study, cardiac MRI evaluation over a anthracyclines).47 De Souza et al also suggested that
period of 16 weeks after anthracycline administration decreased cardiomyocyte size may contribute to an
showed that the acute phase of myocardial injury was increase in ECV.48
characterised by prolongation of T2 relaxation time. The online supplemental contains E-­ figures that
Significant changes in LVEF, ECV and T1 mapping demonstrate the different cardiac MRI parameters in a
occurred only weeks later. T2 relaxation time prolon- case with CTRCD.
gation in the acute phase was correlated with oedema
within the cardiomyocyte. Withholding anthracycline
administration at the time of occurrence of T2 abnor- CLINICAL PRACTICE
malities prevented development of subsequent LV Currently, cardiac follow-­u p of patients with increased
systolic dysfunction.43 risk for CTRCD is based on expert consensus. Teske et
Reports of myocardial mapping in oncology patients al provided an overview about the available evidence
are generally mixed in results; myocardial oedema and clinical practice in our institution which will be
after receipt of anthracycline and/or trastuzumab was referred to in the following section.49 Typically, the
demonstrated in almost half of the patients at 1 or surveillance of adult patients with cancer who will
4 months after initiation of therapy, but LV dysfunc- receive cardiotoxic agents starts before initiation of
tion could not be predicted.34 In a 5-­y ear follow-­u p cancer therapy and ends up to 1 year after last chemo-
study, both LV function and T1 mapping values were therapy dose. The frequency of follow-­u p is based on
within the normal limits. 42 Muehlberg et al described the individual risk profile for CTRCD, which incorpo-
different findings with regard to cardiac MRI values rates parameters such as type and dosage of chemo-
in sarcoma patients shortly after anthracycline-­based therapy, age at time of chemotherapy and presence of
chemotherapy. Within 48 hours after chemotherapy cardiovascular risk factors.49
initiation, native T1 decreased significantly in patients The results of the recently published studies show
who developed CTRCD (LVEF drop >10% points) at that CTRCD can affect multiple parts of the myocar-
the end of the chemotherapy. T1 values normalised dium and therefore reinforce the recommendation of
in all CTRCD cases after treatment completion and a comprehensive and systematic echocardiographic
myocardial T2 mapping values did not significantly assessment of at least LV systolic and diastolic func-
change during chemotherapy.41 The authors suggest tion, LV strain and RV function. 4 It is important to
that development of CTRCD may consist of different use the same imaging modality over time to enhance
phases and therefore the interpretation of cardiac adequate interpretation of serial measurements and
MRI results after anthracycline therapy may be identification of individual CTRCD.4 Since the accu-
adapted to the timing of assessment.41 racy in LV measurements by 3D echocardiography
In addition, a recent study by Altaha et al demon- has expanded in clinical care, this modality is recom-
strated greater temporal differences in T1, T2 and mended for serial LVEF measurements in patients
ECV in patients with HER2-­positive breast cancer with with cancer.4 Regarding myocardial strain, a clear
CTRCD (n=10), defined as >10% reduction in LVEF superiority of 3D STE over 2D STE has not been
to <55% or >15% relative reduction in GLS, compared reported yet, although results of 3D-­d erived strain are
with patients without CTRCD and healthy participants. promising.16 17
However, the results in patients with CTRCD overlap The use of cardiac MRI is recommended as a comple-
with variability in healthy participants, emphasising mentary tool when echocardiography is inconclusive

4 de Baat EC, et al. Open Heart 2021;8:e001506. doi:10.1136/openhrt-2020-001506

 Heart failure and cardiomyopathies

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and when evaluation of other underlying causes of subclinical myocardial changes may precede global
LV dysfunction is indicated. 2 4 Despite the superior LV dysfunction, but it is too early to incorporate these
qualities of cardiac MRI, this modality is (in the Neth- in decision making and warrant therapeutic interven-
erlands) approximately three times more expensive tion. Other novel technical parameters (eg, torsion,
and less available than echocardiography. In our own Tei index) are of potential interest, yet their incre-
institution, CMR is routinely used in case of clin- mental value for clinical purposes has to be explored.
ical CTRCD on transthoracic echocardiography and In addition, more research is needed on diagnostic
considered in case of subclinical CTRCD.49 Further- and risk prediction models that combine echocar-
more, cardiac MRI provides additional diagnostic and diographic measures with other potential predictors
prognostic information in patients with known cardiac such as genetics, cardiovascular risk factors and blood
disease, that is, previous myocardial infarction. biomarkers to improve and individualise cardiac
Heart failure medication is only initiated in adult surveillance and treatment.
patients with evidence of CTRCD, defined as LVEF Myocardial tissue characterisation by cardiac MRI
>10% decline to LVEF <53% or GLS decline of 15% and offers the opportunity to improve follow-­up of the
NYHA ≥II/IV or LVEF <45% on echocardiography.49 myocardium over time and, especially in light of the
potential introduction of anti-­ f ibrosis medication,
may provide important clinical information. There
FUTURE PERSPECTIVES
are only few high-­quality studies that evaluated early
In the future, strain measurements may replace LVEF
(within 3 months after treatment) effects of cancer
for early detection of CTRCD and its incremental
treatment, so more evidence is needed to elucidate
clinical value needs to be further explored. An
its prognostic value. In the future, diffusion-­w eighted
important question remains what the consequences
cardiac MRI images will also be available for the evalu-
are for an asymptomatic patient with reduced strain
ation of the myocardium, which enables evaluation of
and preserved LVEF. The SUCCOUR (Strain sUrveil-
myocyte necrosis during the acute stage and has the
lance of Chemotherapy for improving Cardiovascular
potential to become a new biomarker.
Outcomes) trial is the first (ongoing) randomised
controlled trial in anthracycline-­t reated patients with
cancer at risk of heart failure which compares the CONCLUSION
effect of GLS-­ guided versus LVEF-­ g uided manage- Imaging techniques that allow for detection of early
ment on 3D LVEF 3 years after diagnosis. 50 changes in myocardial function are crucial in the
Parameters as RV function, LV dimensions and follow-­u p of cardiovascular diseases after cardiotoxic
mass, regional function as expressed by basal longi- cancer treatment as exemplified in figure 1. Advanced
tudinal strain, circumferential strain, AS and diastolic imaging techniques may be of additive value due to
measures have shown promising results to suggest that better reproducibility and, even more important, the

Figure 1  Detection of CTRCD using non-­invasive imaging. The progress of CTRCD can be subdivided into different phases.
Multiple non-­invasive modalities play an important role in order to detect CTRCD as early as possible. Interstitial myocardial
changes including oedema and fibrosis shortly after start of chemotherapy can be reflected by tissue characterisation with
cardiac MRI. Thereafter, changes in myocardial function may occur. Myocardial strain is an important parameter of early to
intermediate cardiac impairment which can be measured by echocardiography and MRI. On the long term, months to years
after start of chemotherapy treatment, asymptomatic left ventricle systolic dysfunction may progress to heart failure so follow-­
up based on left ventricular ejection fraction is recommended. CTRCD, cancer treatment-­related cardiac dysfunction; DWI,
diffusion-­weighted imaging; GLS, global longitudinal strain; LVEF, left ventricular ejection fraction; MRI, magnetic resonance
imaging; MUGA, multigated acquisition scan.

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Funding  The authors have not declared a specific grant for this research from any 14 Saijo Y, Kusunose K, Okushi Y, et al. Relationship between regional
funding agency in the public, commercial or not-­for-­profit sectors. left ventricular dysfunction and cancer-­therapy-­related cardiac
Competing interests  None declared. dysfunction. Heart 2020;106:1752–8.
15 Narayan HK, French B, Khan AM, et al. Noninvasive measures
Patient consent for publication  Not required. of ventricular-­arterial coupling and circumferential strain predict
Provenance and peer review  Not commissioned; externally peer reviewed. cancer Therapeutics-­Related cardiac dysfunction. JACC Cardiovasc
Imaging 2016;9:1131–41.
Data availability statement  There are no data in this work. 16 Muraru D, Niero A, Rodriguez-­Zanella H, et al. Three-­dimensional
speckle-­tracking echocardiography: benefits and limitations of
Open access  This is an open access article distributed in accordance with the integrating myocardial mechanics with three-­dimensional imaging.
Creative Commons Attribution Non Commercial (CC BY-­NC 4.0) license, which Cardiovasc Diagn Ther 2018;8:101–17.
permits others to distribute, remix, adapt, build upon this work non-­commercially, 17 Santoro C, Arpino G, Esposito R, et al. 2D and 3D strain for
and license their derivative works on different terms, provided the original work is detection of subclinical anthracycline cardiotoxicity in breast cancer
properly cited, appropriate credit is given, any changes made indicated, and the use patients: a balance with feasibility. Eur Heart J Cardiovasc Imaging
is non-­commercial. See: http://​creativecommons.​org/​licenses/b​ y-​nc/​4.​0/. 2017;18:930–6.
18 Cherata DA, Donoiu I, Diaconu R, et al. Longitudinal strain analysis
ORCID iDs allows the identification of subclinical deterioration of right
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