Monitoring the heart during cancer therapy

Abstract

A growing number of effective cancer therapies is associated with cardiovascular (CV) toxicities including myocardial injury or dysfunction, leading to reduced ventricular function, and increased risk of heart failure. As the timing of administration of cancer treatment is known, the potential for risk stratification pre-treatment, and appropriate surveillance and monitoring during treatment, and intervention with cardio-protective treatment strategies in patients exhibiting early evidence of CV toxicity is an appealing clinical strategy. The field of cardio-oncology has developed, and the application of monitoring strategies using CV biomarkers and CV imaging has been to focus of many studies and is now implemented in dedicated cardio-oncology services supporting oncology centres. In this article, we review the background and rationale for monitoring, the different options and their strengths, weaknesses and where they are helpful in specific cardiotoxic cancer therapies, and the impact in cardio-oncology care.

Full text

Monitoring the heart during cancer therapy
Mohsen Habibian
1,2
and Alexander R. Lyon
2,3
*
1
The Prince Charles Hospital and University of Queensland, Rode Road, Chermside, QLD 4032, Australia;
2
Cardio-Oncology Service, Royal Brompton Hospital, Sydney Street, Chelsea, London, SW3 6NP, UK; and
3
National Heart and Lung Institute, Imperial College London, Cale Street, Chelsea, London, SW3 6LY, UK
KEYWORDS
Heart failure;
Cancer;
Cardio-oncology;
Monitoring
A growing number of effective cancer therapies is associated with cardiovascular (CV)
toxicities including myocardial injury or dysfunction, leading to reduced ventricular
function, and increased risk of heart failure. As the timing of administration of cancer
treatment is known, the potential for risk stratification pre-treatment, and appropriate
surveillance and monitoring during treatment, and intervention with cardio-protective
treatment strategies in patients exhibiting early evidence of CV toxicity is an appealing
clinical strategy. The field of cardio-oncology has developed, and the application of
monitoring strategies using CV biomarkers and CV imaging has been to focus of many
studies and is now implemented in dedicated cardio-oncology services supporting on-
cology centres. In this article, we review the background and rationale for monitoring,
the different options and their strengths, weaknesses and where they are helpful in
specific cardiotoxic cancer therapies, and the impact in cardio-oncology care.
Introduction
In recent years, cancer treatment is becoming more effec-
tive with the advent of novel agents targeting new path-
ways, receptors and activating the immune system to
target the cancer cells. These advances have improved the
rates of successful treatment and survival from cancer.
However, the rate of complications related to these thera-
pies has also increased.
1
Cardiovascular (CV) complications
are a common and important side effect which not only has
the potential to affect the quality of life and longevity in
cancer survivors but also leads to interruption of effective
anticancer treatments leading to worse cancer outcomes.
2
Cardiovascular diseases are frequently the leading cause of
non-cancer-related mortality. For example, survivors of
cancers diagnosed in childhood,
3–6
patients with breast
cancer
7
and many other cancers, the risk of developing CV
complications persists for years after treatment with
anthracycline chemotherapy (AC) or radiotherapy to the
chest.
8
During cancer therapy, patients who have pre-
existing CV disease and even CV risk factors, display a
higher risk of cardiotoxicity from AC and other cardiotoxic-
targeted cancer therapies [e.g. vascular endothelial
growth factor inhibitors (VEGFi), BCr-ABl inhibitors, pro-
teasome inhibitors (PIs), Raf-MEK inhibitors, and
Gonadotrophin-releasing hormone (GnRH) receptor ago-
nists]. Cancer treatment pathways are scheduled which
allows a unique opportunity for a baseline pre-treatment
risk assessment and monitoring of CV toxicity allowing
pre-emptive treatment.
9
This approach requires an under-
standing of the short- and long-term CV complications
encountered with each specific oncology treatment, paired
with appropriate cardiology knowledge, allowing for path-
way design, diagnosis, and management of cardiac compli-
cations resulting as a consequences of cancer treatment on
the CV system, or as a result of the direct involvement of
the cancer in the heart, in the new subspecialty of cardio-
oncology.
10
Establishing and developing such a specialized
field requires close collaboration between cardio-
oncologists, oncologists, and haemato-oncologists. This
multidisciplinary approach has been shown to yield better
prognostic outcomes in patients suffering from numerous
different types of cancer.
11,12
The purpose of this subspeci-
alty is to prevent the development and minimize the pro-
gression of CV complications by guiding treatment
therapies and interventions tailored to the patient.
*Corresponding author. Tel: þ44 (0) 207 352 8121 (ext 82396),
Fax: þ44 (0) 207 351 8776, Email: a.lyon@ic.ac.uk
Published on behalf of the European Society of Cardiology. V
CThe Author(s) 2019.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence
(http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in
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European Heart Journal Supplements (2019) 21 (Supplement M), M44–M49
The Heart of the Matter
doi:10.1093/eurheartj/suz230
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Cancer drug therapies can affect many structures in the
heart, including myocardium [causing inflammatory or
non-inflammatory left ventricular dysfunction and heart
failure (HF)], conduction system (heart block), electro-
physiology (tachy- or bradyarrhythmias and QT-prolonga-
tion), pericardium, coronary arteries (raising issues like
myocardial infarction, vasospasm, or accelerated athero-
sclerosis), valves (especially after high-dose radiotherapy
to the valve tissue), the pulmonary circulation causing pul-
monary hypertension, and the systemic arterial and venous
circulation leading to arterial hypertension, peripheral vas-
cular disease, and venous thromboembolism. Chest-di-
rected radiotherapy can increase coronary artery disease
or cause fibrotic changes predominantly to the valves;
pericardium or myocardium and, therefore, monitoring in
survivors who have received high-dose radiation to the
heart should consider these multiple CV diseases. Cancer
patients should also have serial assessment of modifiable
CV risk factors (cholesterol, hypertension, diabetes, smok-
ing status, and body mass index) and the risks addressed
according to the CV prevention guidelines for high-risk
patients.
13
Monitoring for CV disease during and after cancer ther-
apy will be discussed in two sections (See Figure 1). In the
first part, the general considerations are provided for all
cancer patients. In the second section, cancer treatments
with specific CV side effect profiles, requiring targeted CV
screening, and follow-up with individualized surveillance
programme are discussed. The complexity of this field for
each cancer therapy with a CV toxicity profile and how
pathways of care for low-, moderate-, and high-risk
patients is beyond the scope of this article, and we refer
the reader to the forthcoming series of position statements
from the Heart Failure Association (HFA) of the European
Society of Cardiology which will present Baseline risk
stratification proformas, detailed biomarker and imaging
surveillance pathways and treatment strategies for a range
of effective cancer therapies with potential cardiotoxicity.
Baseline cardiovascular risk assessment and
cardio-oncology follow-up
A baseline risk assessment is advised for patients scheduled
to receive a cancer therapy with potential CV toxicity. This
should be provided by the oncology and haemato-oncology
services in co-ordination with their local cardiology or
cardio-oncology service.
Assessment of baseline CV risk before cancer therapies
which are potentially cardiotoxic is advisable. Baseline risk
is based on several patient-related factors, treatment-re-
lated factors, and cancer-related factors. Young children
or individuals older than 65years, pre-existing conven-
tional CV risk factors (hypertension, diabetes, dyslipidae-
mia, and smoker), and antecedent heart disease (like left
ventricular dysfunction or coronary artery disease)
increases the risk of CV complications. Additionally, type of
treatment used, cumulative dose (AC and trastuzumab),
combination therapy (such as AC and HER2 receptors or
dual immunotherapy agents use), or intensive or acceler-
ated regimens put the patientat higher risk of cardiac com-
plications. The type and location of the cancer are
important. For instance, mediastinal tumours requiring ra-
diotherapy increases the cardiac side effects if the heart is
in the radiation field.
14
Pathways should ensure high-risk patients are referred
and reviewed promptly by the cardiology or cardio-
oncology service and guidance on monitoring during the
planned cancer therapy is provided with a schedule person-
alized to the patient, their CV risk factors and pre-existing
CV disease, the proposed cancer treatment and the context
(metastatic vs. curative intent, prognosis with and without
cancer treatment, alternative non-cardiotoxic cancer ther-
apies). Cardiac symptom review before and during cancer
treatment are important in addition to monitoring cardiac
function and injury directly via biomarkersand imaging.
12
Imaging assessment
Echocardiography
Echocardiography is a first-line cardiac imaging technique
with advantages including its availability, assessment of
multiple elements of cardiac function beyond left ventricu-
lar ejection fraction (LVEF), relatively cheap cost, and
it is radiation-free allowing multiple scans safely.
Echocardiographic assessment of cardiotoxicity allows de-
tection during and in the 12 months after treatment, and in
high-risk patients may be used for intermittent surveillance
for life. Most focus has been on monitoring LVEF is important
in monitoring the cancer patients during or after the treat-
ment, and a pre-treatment echocardiography in the high-
risk patients provide a baseline for further comparison.
12
Cancer therapeutics-related cardiac dysfunction
(CTRCD) has a range of definitions, from oncology trials to
cardiology studies and registries, which has added confu-
sion to the field. The joint EACVI-ACC imaging position
Monitoring
•ECG
•Standard Echo
•Advanced Echo: Strain
studies (GLS), Tissue
Doppler, 3D volumes
•Stress Echo
•CMR
•Biomarkers
Baseline
Cardiovascular
Assessment
Early detecon of
cardiotoxicity
Diagnosis of
cancer or
evaluaon
of cancer
progress
Early signs of CTRCD:
Commence cardioprotecve
medicaons and connue
cancer treatment
Moderate CTRCD:
Opmisaon of cardiac
medicaon, provisional
interrupon of cancer
treatment and reassess
Severe CTRCD:
Interrupon of
cancer treatment,
cardiac
opmisaon,
reassess and
balance cancer
treatment,
prognosis and
cardiac risks
Figure 1 Summary of monitoring the heart receiving cancer treatment.
Monitoring the heart during cancer therapy M45
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statement proposed one definition, the LVEF is reduced by
more than 10% from the baseline or it decreased to the
value <53%, and this should be confirmed in two consecu-
tive echocardiography assessments with 2–3 weeks apart.
15
However, there are several limitations of this type of defi-
nition. Left ventricular (LV) volumes and LVEF are ideally
measured by Simpson’s biplane method. However, LVEF is
both load- and heart rate-dependent in many patients.
Intravascular volume in the cancer patients is quite vari-
able, as they sometimes receive large amount of intrave-
nous fluidsat the time of chemotherapy, or are dehydrated
due to vomiting or diarrhoea. Sympathetic tone varies and
may be elevated due to stress, anxiety, and/or pain. These
changes all affect LVEF and introduce variability and poten-
tial error. Cancer patients may have suboptimal acoustic
windows form prior chest surgery or radiotherapy.
Contrast-enhanced echocardiography is useful in more ac-
curate assessment of LVEF; however, the LV volume whilst
using contrast may be overestimated and contrast obscure
other detailed measurements. Three-dimensional ejection
fraction may help to improve accuracy of measurements
but cannot always be acquired due to image quality. When
three-dimensional echocardiography is performed, it is
critical to recognize that the normal references for the car-
diac chambers and LVEF is different from two-dimensional
measurements. Three-dimensional imaging is highly based
on the two-dimensional image quality and it is not helpful
in the patients with difficult acoustic windows.
Another technically challenging issue is that LVEF assess-
ment cannot identify early cardiotoxicity in treatments
like anthracyclines
16
and when depressed LVEF is diag-
nosed, significant myocardial injury has already occurred is
more likely to be irreversible.
17
Tissue Doppler assessment and diastolic function, includ-
ing septal and lateral E’, S’, and mitral annulus plane
systolic excursion M-mode (MAPSE) as well as mitral inflow
E waves measurements have all been studied in different
trials and can add incremental value in monitoring the
heart in cancer patients, and at times it has helped to iden-
tify the cardiotoxicity in earlier stages. Although there is
no definite cut-off point to determine normality for these
measurements in cancer patients, serial assessment may
identify early cardiotoxicity. The transmitral E/Aratio may
be an independent predictor of cardiotoxicity in some stud-
ies although this has not been reproduced in other
studies.
18
Speckle tracking, especially to measure left ventricular
global longitudinal strain (GLS) may be helpful in detecting
subclinical LV dysfunction, and the values should be com-
pared against the baseline and more studies are in process
to elucidate the details. Impairment in GLS <8% probably
does not have clinical consequences. However, worsening
of >15% has been proposed as a clinically significant, but in
the opinion of the authors, this is only relevant if it also
falls into the abnormal GLS range. In addition, it is critical
that serial monitoring is performed with echocardiography
machines from the same vendor so the scale remains the
same.
15
Emerging data suggest that GLS reduction may be
relevant in specific cancer populations including those re-
ceiving immune checkpoint inhibitors (ICIs) and paediatric
cancer survivors during long-term follow-up.
19,20
In some
cancer populations, a reduction in GLS appears to predict
future fall in LVEF, but as a more sensitive imaging tech-
nique it must be applied cautiously (e.g. effective oncology
treatments must not be stopped based on a reduction of LV
GLS alone). More studies are required to prove impairment
in GLS can change outcomes and this will be addressed in
one cancer population in the SUCCOUR trial.
Monitoring valvular disease in cancer survivors who have
been exposed to high doses of cardiac radiation may be ap-
propriate. Prospective studies are absent, partly due tothe
long latency between treatment exposure and clinically
significant valve disease. Five yearly echocardiographic
surveillance from 5 years post-treatment may be consid-
ered, with more frequent assessment if abnormalities of
valvular function are detected. During and after treat-
ment, if infective endocarditis is suspected, transoesopha-
geal echocardiography may be appropriate. Mitral
regurgitation may be primary due to radiation-related
damage, or secondary to LV dysfunction. A similar principle
is also relevant for tricuspid regurgitation as primary
or secondary to right ventricular (RV) dilatation.
Radiotherapy in younger patients causes direct valvular in-
jury with fibrotic changes in intracardiac valves causing
stenosis or regurgitation and monitoring valvular disease is
important in these patients. In older patients with pre-
existing valve disease, lower radiation doses may acceler-
ate the underlying disease. When valvular dysfunction is
diagnosed, more frequent monitoring with serial echocar-
diography is recommended.
Pericardial diseases are also more common in cancer
patients after radiation therapy to the heart, and echocar-
diography provides opportunity to assess pericardial effu-
sion or consequences like tamponade or constrictive
physiology with preload challenge if equivocal results at
rest are detected.
Stress echocardiography may be applied for several indi-
cations. First is in the assessment for flow-limiting coronary
disease in patients at moderate or high risk before major
cancer surgery or cancer treatments which may potentially
cause myocardial ischaemia, including fluorpyrimidines
(5-fluorouracil and capecitabine) or VEGFi.
21
Serial assess-
ment of contractile reserve has been studied but is not
validated for routine clinical practice although it may be
helpful in early detection of subclinical cardiac dysfunc-
tion. Stress echocardiography is not only valuable in CV
prognosis but provocatively it may also helpful in estima-
tion of non-cardiac cancer death.
22
Endomyocardial biopsy
In the past considered as the most specific modality for di-
agnosis of cancer therapeutics-related cardiotoxicity.
However, owing to its invasive nature and inherent risks, it
is considered generally as a last line of investigation, espe-
cially with the advent of other modalities for monitoring
the heart like advanced echocardiography and biomarkers.
However, it is becoming increasingly important for the di-
agnosis or exclusion of ICI-related myocarditis in borderline
cases with discordant biomarker and imaging findings to
guide future ICI treatment.
M46 M. Habibian and A.R. Lyon
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Cardiac magnetic resonance
Cardiac magnetic resonance (CMR) provides detailed as-
sessment of LV and RV function and is the best imaging mo-
dality to evaluate presence or absence of fibrosis,
infarction, myocarditis, and amyloidosis, as well as pericar-
dial anatomy and inflammation, and assessment of intra-
cardiac masses. However, CMR has several important
limitations, including cost, accessibility, acquisition time,
contraindications in the patients with implanted metal
works, quality in patients with fast heart rates, AF or fre-
quent ectopy, and difficulties in the patients suffering from
claustrophobia or advanced anxiety.
MUGA
Multiple-gated acquisition scan (MUGA) was initially the
standard modality for early assessment of serial LVEF and
detection of subclinical left ventricular dysfunction prior
to the clinical HF. It has the advantage of being reproduc-
ible and useful in the patients with difficult acoustic win-
dows which makes the transthoracic echocardiography
difficult and is widely available with costs comparable with
other modalities. However, MUGA has drawbacks, particu-
larly, the cumulative dose of radiation, and inability to pro-
vide information about other cardiac elements like LV
diastolic function, right ventricle, PA pressure, valvular
function, or left atrium dimensions.
23
Cardiac biomarkers
Cardiac biomarkers are readily and widely available with
high precision, accuracy, and clear cut-off points for a
range of cardiac diseases, e.g. acute coronary syndromes.
Cardiac biomarkers including cardiac troponin (cTn) and
natriuretic peptides [brain natriuretic peptide (BNP) and
N-terminal portion of proBNP (NT-proBNP)] have been stud-
ied for early detection of cardiac dysfunction.
24
Cardiac
troponin’s are markers of cardiac injury, and in many stud-
ies showing the patients receiving AC with elevated tropo-
nin levels are at higher risk of cardiac events and
developing cardiotoxicity, and the magnitude and duration
of this elevation are important in cardiac prognosis after
completing AC.
25
The value of cTn in newer cancer drugs
like trastuzumab in treatment of breast cancer has also
been explored, although many of these patients have also
received AC.
26
Brain natriuretic peptide is more sensitive
than cTn during trastuzumab, VEGFi, and PI at detecting
early LV dysfunction and predicting function clinical
cardiac adverse events. Emerging data suggest BNP or
NT-proBNP may also be helpful in detecting ICI-medicated
cardiotoxicity. In an unselected population of all CV toxic-
ity from ICI, only 46% of the patients had positive troponin
levels but all (100%) had elevated BNP. However, this may
reflect different clinical practice regarding biomarker
measurement and more detailed studies are required. In
high-risk patients scheduled to receive potentially cardio-
toxic cancer treatments known to cause HF regular moni-
toring of cardiac biomarkers including cTn and natriuretic
peptides (NPs) should be considered for early detection of
cardiac dysfunction.
Anthracycline chemotherapy
Anthracycline chemotherapy, including doxorubicin, epiru-
bicin, daunorubicin, idarubicin, and anthracenediones
(mitoxantrone and pixantrone) cause cumulative dose-
dependent cardiotoxicity and dysfunction, AC’s cause cardi-
omyocyte damage via increased reactive oxygen species
and topoisomerase-IIbinhibition.
27
At the cellular level, it
causes vacuolar deformation before myofibrillar dysfunction
and cellular apoptosis.
28
If left late this leads to irreversible
damage and hence early measurement of cTn is helpful to
detect early myocardial injury before irreversible left ven-
tricular systolic dysfunction (LVSD) and HF develops.
29,30
HER2-targeted therapy
Trastuzumab, pertuzumab, T-DM1, lapatinib, and neratinib
are the HER2-targeted therapies with inhibit the HER2 re-
ceptor and improve prognosis in HER2þearly invasive and/
or metastatic HERþbreast cancer. Heart disease initiated
cardiac HER2 expression in a mechanism for cardioprotec-
tion and stabilization, and hence HER2 inhibitors cause LV
and/or RV dysfunction. In most cases, HER2-targeted ther-
apy-mediated cardiac dysfunction is reversible by interrup-
tion of the therapy and administration of cardioprotective
medications. However, interruption of HER2 targeted ther-
apies may lead to worse cancer outcomes, particularly in
metastatic HER2þbreast cancer and so preventing inter-
ruptions through monitoring is an appealing strategy.
Regular monitoring with echocardiography for early detec-
tion is recommended and recent studies suggest two new
approaches. The first is to use baseline cTn pre-treatment
and serial surveillance of both GLS and NPs during treat-
ment as a sensitive strategy. The second is to continue tras-
tuzumab in patients where the LVEF falls to 40–49%
providing the patient is clinically stable and with imple-
mentation of appropriate cardioprotective medication.
31
Vascular endothelial growth factor inhibitors
Vascular endothelial growth factor inhibitors (VEGFi) have
a relatively higher rate of CV side effects, particularly, the
more non-specific tyrosine kinase inhibitors (e.g. Sunitinib
and Sorafenib). The most common complications include
arterial hypertension, ischaemic events, arrhythmias due
to QT-prolongation, and cardiac dysfunction, which may be
multifactorial, including both hypertensive HF and direct
cardiotoxicity, particularly, in patients with pre-existing LV
dysfunction or hypertrophy. Therefore, a baseline risk as-
sessment in all cancer patients scheduled to receive a
VEGFi is recommended, with regular cardiac monitoring in
moderate and high-risk patients using echocardiography
and NPs. Regular blood pressure monitoring with home
blood pressure diaries, and electrocardiograms (ECG’s) in
clinic to measure QTc intervals,are recommended.
BCr-ABl TKI’s
BCr-Abl TKIs are predominantly used in the treatment of
chronic myeloid leukaemia with Imatinib being the
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characteristic agent in this group, which has minimal car-
diac side effects. However, second-generation therapies
such as Dasatinib and Nilotinib, and the third-generation
BCr-Abl TKI Ponatinib have significant CV toxicities.
Nilotinib accelerates the atherosclerotic process and
causes accentuation in baseline CV risk factors, to the ex-
tent that peripheral arterial disease leading to limb ampu-
tation has been reported. It also causes QTc-interval
prolongation. Monitoring requires regular assessment of
standard CV risk factors, including cholesterol, HbA1c,
blood pressure, and ECGs to measure QTc. Dasatinib may
cause pulmonary hypertension and/or HF and serial echo-
cardiography to address both LV function and PA pressure is
recommended in moderate- and high-risk cases (baseline
PA elevation and baseline LV dysfunction). Dasatinib cause
pleural effusion in up to 28% of cases with an unknown
mechanism but it does not appear to be cardiac. Bosutinib
has lower rates of CV complications, all of which in the
studies could be managed medically without the need for
discontinuation of Bosutinib. Ponatinib, which also being
used in the trials for acute lymphoblastic leukaemia, has a
relatively high risk of CV toxicity. This includes an increased
risk of occlusive arterial and venous occlusive events.
Ponatinib also causes HF in a dose-dependent effect and
myocardial infarction. Cardiac and CV risk factor monitor-
ing should be performed to address these potential side
effects and optimize CV risk factor control.
32
RAF/MEK TKI’s
RAF and MEK inhibitors are pro-survival pathways in various
cancers including melanoma and thyroid cancers. In combi-
nation, they have improved survival in Raf-mutant mela-
noma and other Raf-mutant cancers. Recent data have
clarified that HF or LVSD is caused by combination Raf- and
MEK inhibitors in 5–10% of patients.
33
Regular monitoring
for early detection of cardiac dysfunction with serial echo-
cardiography, biomarkers, and ECG’s may be considered in
the patients receiving these agents but more research is
required.
Immune checkpoint inhibitors
Immune checkpoint inhibitors ICIs are increasingly used to
treat a variety of neoplasms with important benefits.
Immune checkpoint inhibitor-mediated cardiotoxicity oc-
curring most commonly in the first few cycles, with inflam-
matory CV toxicities including myocarditis, pericarditis,
and vasculitis. LV dysfunction including cardiogenic shock,
and malignant ventricular arrhythmias may occur in
patients with myocarditis with high mortality rates of 25–
50%.
34–36
The optimal monitoring strategy has not been
identified, but ECG and biomarker (cTn and NP) monitoring
in the first few cycles may be helpful. Cardiac complica-
tions are more prevalent in combination immunotherapy
settings, for example, the combination of Nivolumab and
Ipilimumab, or an ICI plus a VEGFi. The effects of ICI’s are
variable in different individuals. They have the potential to
cause heart block, tachyarrhythmias, cardiac dysfunction,
pericarditis, acute coronary syndrome, or vasculitis.
Monitoring may consist of regular ECG’s, cardiac bio-
markers, and echocardiography. In case of LV dysfunction,
CMR is very important in diagnosing the underlying aetiol-
ogy and distinguishing the inflammatory from non-
inflammatory dysfunction, which has different treatment
options and implications in cancer therapy.
Ibrutinib
Ibrutinib is a first-generation Bruton Tyrosine Kinase inhibi-
tor used in B-cell cancers, demonstrating cardiotoxicity in-
cluding a high risk of new atrial fibrillation and a small
increased risk of ventricular arrhythmias and sudden car-
diac death.
37
Monitoring for new AF with serial ECGs, or
other technologies for cardiac rhythm monitoring, may be
considered.
Conclusion
Cardiovascular monitoring of selected cancer patients re-
ceiving cardiotoxic cancer treatments, who are at higher
risk, is a logical clinical strategy for the early detection of
cardiac dysfunction if this leads to implementation of car-
dioprotective strategies to allow effective cancer thera-
pies to continue safely. More trials are required to identify
the optimal monitoring strategy for each cancer treat-
ment, including which modalities (imaging, biomarkers,
and combination) and frequency, with the goal of improv-
ing both cancer and CV outcomes. Expert consensus and po-
sition papers from the HFA will address these challenges
and provide clinical pathways in the near future based on
the experience and limitedevidence available.
Conflict of interest: Dr A.R.L. received speaker, advisory board or
consultancy fees and/or research grants from Pfizer, Novartis,
Servier, Amgen, Takeda, Roche, Janssens-Cilag Ltd, Clinigen
Group, Eli Lily, Eisai, Bristol Myers Squibb, Ferring Pharmaceuticals
and Boehringer Ingelheim. M.H. has no conflicts to declare.
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