RIESGO CARDIOVASCULAR CARDIO-ONCOLOGÍA

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Eur J Heart Fail. Author manuscript; available in PMC 2021 April 03.
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Published in final edited form as:

Eur J Heart Fail. 2020 November ; 22(11): 1945–1960. doi:10.1002/ejhf.1920.
Baseline cardiovascular risk assessment in cancer patients

scheduled to receive cardiotoxic cancer therapies: a position
statement and new risk assessment tools from the Cardio-
Oncology Study Group of the Heart Failure Association of the
European Society of Cardiology in collaboration with the
International Cardio-Oncology Society
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A full list of authors and affiliations appears at the end of the article.
Abstract
This position statement from the Heart Failure Association of the European Society of Cardiology
Cardio-Oncology Study Group in collaboration with the International Cardio-Oncology Society
presents practical, easy-to-use and evidence-based risk stratification tools for oncologists,
haemato-oncologists and cardiologists to use in their clinical practice to risk stratify oncology
patients prior to receiving cancer therapies known to cause heart failure or other serious
cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients
prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2-targeted
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therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third
generation multi-targeted kinase inhibitors for chronic myeloid leukaemia targeting BCR-ABL,
multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and
MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas
will allow clinicians to stratify cancer patients into low, medium, high and very high risk of
cardiovascular complications prior to starting treatment, with the aim of improving personalised
approaches to minimise the risk of cardiovascular toxicity from cancer therapies.
Keywords
Risk factors; Cardio-oncology; Cardiotoxicity; Heart failure; Risk prediction
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Introduction
There is a growing epidemic of cardiovascular disease (CVD) in cancer patients during and
after cancer treatment. Improved cancer-related survival and the development of more
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use,
distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
*
Corresponding author. Cardio-Oncology Service, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK. Tel: +44 20 7352
8121, [email protected].
Supplementary Information
Additional supporting information may be found online in the Supporting Information section at the end of the article.
Lyon et al. Page 2
targeted molecular therapies, in addition to the continued use of anthracycline chemotherapy,

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have resulted in a significant increase in both current and previously treated cancer patients
presenting to cardiology services with CVD.1 The frequency of cardiovascular (CV)
problems is higher in cancer patients who are receiving or who have previously received
cancer treatments with a known CV toxicity profile. The average age of oncology patients is
also increasing with the general ageing of the population, which is in part due to improved
survival from CVD. Therefore, there are a rising number of patients who present to
oncology and haemato-oncology services not only with a new cancer diagnosis but also with
pre-existing CVD or risk factors for CVD.1 This poses a particular challenge when
considering evidence-based oncology treatments that improve survival but impart a higher
risk of CV toxicity.
Current oncology practice, including treatment planning and protocols for cancer treatments
with potentially CV toxicity, provides unique opportunities to comprehensively assess CV
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health before initiation of cancer treatment. This allows cardiologists and other healthcare
professionals, working in partnership with oncologists and haemato-oncologists, to optimise
the management of pre-existing CVD and modifiable CV risk factors with the aim of
reducing the risk of CV complications during and after cancer treatment. The assessment
occurring prior to the initiation of cancer treatment and in patients without overt CVD or
previous cardiotoxicity can be considered a primary prevention strategy while interventions
in patients with pre-existing CVD or evidence of prior CV toxicity fall into the category of
secondary prevention (Figure 1). Specialist care of CVD in cancer patients is now offered by
dedicated cardio-oncology services which have emerged over the last 10 years.2,3 This
multidisciplinary approach has the potential not only to reduce morbidity and mortality from
CVD, but also to improve cancer outcomes by reducing interruptions in cancer treatment
due to CV events and facilitate treatment options with greater potential CV risk. The aim of
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a multidisciplinary cardio-oncology approach is to support best practice, guideline-directed

cancer care by maintaining cancer patients on effective therapies for as long as
recommended, and increase the proportion of cancer patients who complete their cancer
treatment without interruption for CVD.
Many studies have identified a range of parameters that contribute to CVD risk, but these
risk factors are not routinely and systematically assessed in oncology and haemato-oncology
units at the time of cancer diagnosis or during cancer treatment (Figure 2). Several
guidelines and expert position statements have been published by professional societies of
cardiology, oncology and cardio-oncology focussed on CVD in cancer patients and all
recommend baseline CV risk assessment in cancer patients prior to starting potentially
cardiotoxic cancer treatments.1,4–6 However, there is no standardised system or risk
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assessment tool to facilitate CV risk stratification in oncology and haemato-oncology

services.
The Cardio-Oncology Study Group from the Heart Failure Association (HFA) of the
European Society of Cardiology (ESC) hosted a workshop in collaboration with the
International Cardio-Oncology Society (ICOS) dedicated to the development of ‘Baseline
CV risk stratification proformas’ that can be used by oncology and haemato-oncology teams
to stratify cancer patients for CV risk before initiation of potentially cardiotoxic cancer
Lyon et al. Page 3
therapies (Table 1). This position statement summarises the evidence reviewed at the
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workshop and subsequently by the co-authors of this paper, and proposes new HFA-ICOS
baseline CV risk stratification proformas for seven classes of cancer therapies which are
associated with significant risk of CVD, including but not limited to heart failure (HF).
General principles
The assessment of baseline CV risk in cancer patients before starting potentially CV toxic
cancer therapies is based on the following core principles:
• Risk is a continuous variable.
• Multiple CV risk factors may co-exist in an individual cancer patient and they
have an additive or synergistic contribution to CV risk.
• Evidence or expert consensus exists that a parameter contributes to future risk of

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CVD and justifies its inclusion in the baseline CV risk assessment proforma.
• Increased absolute risk (rather than relative risk) is the most relevant for
individual patient-based treatment decisions and the relative importance
attributed to these risk factors.
• Cancer patients identified at increased risk of cancer treatment-related CV

toxicity using these baseline CV risk assessment proformas should not have their
evidence-based cancer treatment withheld unless they are identified at high or
very high risk and after multidisciplinary discussion between the treating
oncologist/haematologist and cardiologist.
• Baseline CV risk stratification should be completed promptly and should not

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delay starting cancer treatment (unless high or very high risk or pre-existing
CVD is present).
• Decisions to withhold effective but potentially cardiotoxic cancer treatments in

cancer patients at high or very high risk of CVD should only be made after
multidisciplinary team discussion between the treating oncologist/haematologist
and cardiologist balancing treatment efficacy vs. safety and CV risk for a
particular individual.
• Decisions regarding switching to alternative less cardiotoxic cancer treatments in

cancer patients identified at high or very high risk of CVD should only be made
after multidisciplinary team discussion between the treating oncologist/
haematologist and cardiologist, balancing treatment efficacy vs. safety and CV
risk for a particular individual.
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• The cancer patient should be informed and participate in the decision making
process and be informed of their baseline CV risk level.
• Cardiovascular treatment interventions should be considered to mitigate CV risk

in cancer patients when identified.
• Pathways of care should exist within an institution using these proformas so that
patients with increased CV risk (medium, high or very high) have their pre-
Lyon et al. Page 4
existing CVD and modifiable CV risk factors reviewed and optimised by a

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suitable healthcare professional (e.g. cardio-oncology service, cardiologist or

primary care/family physician) depending on the nature of the risk, the
cardiotoxic treatment planned and healthcare system.
• Baseline CV risk assessment proformas should be easy to understand and

implement in oncology and haemato-oncology services.
• The application and impact of baseline CV risk assessment proformas can be

assessed using an appropriate clinical audit and review.
Design and application of baseline cardiovascular risk proformas

Several cancer drug therapies associated with clinically important rates of CV toxicity
during or after treatment exposure are summarised in Table 1. The authors acknowledge that
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other cancer therapies are associated with CV risks (e.g. radiation therapy, stem cell
transplantation); however, these are beyond the scope of this article. There is growing use of
immune therapies in oncology, and there is now considerable evidence of CV toxicities from
immune checkpoint inhibitors (ICIs) and emerging information of HF complicating cytokine
release syndrome following chimeric antigen receptor T (CAR-T) cell therapies for various
cancers.7–9 Whilst no evidence currently exists regarding which clinical, imaging and
laboratory parameters may identify patients at higher risk, given the severity of these
complications we recommend all patients scheduled to receive ICI or CAR-T therapy have a
baseline echocardiogram, electrocardiogram (ECG) and measurement of cardiac troponin
and a natriuretic peptide, which serve as a baseline reference if new cardiac complications
develop.
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Baseline CV risk assessment proformas have been developed for seven cardiotoxic cancer
therapy classes known to cause a range of CV toxicities including left ventricular
dysfunction (LVD) and HF (Tables 2–8).10–68 The risk is estimated for all CV complications
from the drug class, e.g. left ventricular dysfunction, QTc prolongation and arrhythmias,
vascular events including myocardial infarction (MI) and hypertension:
• Anthracycline chemotherapy: the main CV complications of anthracycline

chemotherapy are LVD and HF, and atrial and ventricular arrhythmias.19,69
• HER2 targeted therapies: the main CV complications of HER2 targeted therapies

are LVD and HF, and systemic hypertension.44,70,71
• Vascular endothelial growth factor (VEGF) inhibitors [these agents are also
known as angiogenesis inhibitors or VEGF tyrosine kinase inhibitors (TKIs) as
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many act via multi-targeted inhibition of tyrosine kinases]: the main CV

complications of VEGF inhibitors are systemic hypertension, LVD and HF, QTc
prolongation and arterial thrombosis including MI.48,53,57,72
• Multi-targeted kinase inhibitors for chronic myeloid leukaemia (CML) targeting

BCR-ABL (often called BCR-ABL TKIs): the main CV complications of multi-
targeted kinase inhibitors for CML targeting BCR-ABL include arterial
thrombosis leading to MI, stroke and peripheral arterial occlusive disease
Lyon et al. Page 5
(ponatinib), venous thromboembolism, systemic hypertension, LVD and HF,

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accelerated atherosclerosis (ponatinib and nilotinib), QTc prolongation

(nilotinib) and pulmonary hypertension (dasatinib).59,62,73–78
• Proteasome inhibitors (PIs) and immunomodulatory drugs (IMIDs): the main CV

complications of PIs and IMIDs in combination are LVD and HF, ischaemia and
MI, atrial and ventricular arrhythmias, venous thromboembolism and arterial
thrombosis.66,67,79
• Combination RAF and MEK inhibitor treatment: the main CV complications of

RAF and MEK inhibitors are LVD, HF and systemic hypertension for all
combinations and QTc prolongation for one combination (vemurafenib and
cobimetinib).80,81
• Androgen deprivation therapies (ADT) for prostate cancer treatment including

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gonadotropin release hormone (GnRH) agonists: ADT are associated with an

increased risk of diabetes mellitus, hypertension and atherosclerosis (see below).
82–84
• Immune checkpoint inhibitors: myocarditis including fulminant myocarditis,

non-inflammatory HF, ventricular arrhythmias, atrio-ventricular block, sudden
cardiac death, acute coronary syndromes including atherosclerotic plaque rupture
and vasculitis.
The first six proformas each comprise of a single table with five columns on one page. This
can be printed or accessed electronically, completed by the appropriate oncology or
haemato-oncology healthcare professional with the patient, and filed in the patient’s medical
records (paper or digital):
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• Column 1 lists the CV risk factors
• Column 2 is the box to complete if present (yes/no)
• Column 3 is the weighting of the risk factor (medium, high or very high)
• Column 4 has the level of evidence (LoE) supporting the inclusion and weighting
based on the standard LoE definitions used in professional cardiology and
oncology guidelines; and
• Column 5 has references for the publications providing evidence for the risk
factor having predictive value pre-treatment for future CV adverse events which
supports inclusion and level of risk weighting.
The conceptual background of these recommendations is that both patient-related as well as

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therapy-related factors contribute to the CV risk.1,85 The clinical and demographic variables
contributing to increased CV risk can be divided into risk factor classes which are similar for
the six cancer-related treatments associated with CVD and HF in particular. The CV risk
factor classes included in the first six proformas are:
• Pre-existing CVD
• Elevated circulating cardiac biomarkers pre-treatment (if measured)
Lyon et al. Page 6
• Demographic and co-existing medical conditions recognised as CV risk factors

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• Previous cardiotoxic cancer treatment
• Lifestyle-related CV risk factors.
Each risk factor class includes a range of risk factors or variables identified as contributing
to CV risk for patients receiving the specific cancer therapy according to the evidence
available and expert opinion.
Once completed, a risk level can be calculated from the summary using the following simple
rules:
1. Patients with no risk factors are ‘low risk’
2. Patients with one or more risk factors are categorised according to the highest
risk factor present:
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• Patients with one or more very high risk factors—their risk level is
‘very high’
• Patients with one or more high risk factors—their risk level is ‘high’
3. Medium risk factors are given a point weighting as medium1 or medium2
• Patients with one medium1 risk factor only are ‘low risk’
• Patients with a single medium2 risk factor or more than one medium1
risk factor with points totalling 2–4 are ‘medium risk’
• Patients with several medium risk factors with points totalling 5 or

more points are ‘high risk’
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Evidence for defining the absolute risk is limited or absent for each risk factor for every drug
class. Based on discussion and expert opinion, the risk of future cardiotoxicity for each of
the risk groups can be considered as follows: low risk <2%, medium risk 2–9%, high risk
10–19%, very high risk ≥20%. These should be considered a guide and future studies are
needed to validate and refine these ranges and risk weighting.
The seventh baseline CV risk assessment proforma relates to ADT including GnRH agonists
and other anti-androgens (e.g. 17α-hydroxylase inhibitors) used for prostate cancer. The
risks relate to the development of atherosclerotic vascular disease, and there are several
established CV risk calculators for MI and stroke associated with atherosclerosis (Table 9
and ADT baseline CV risk assessment proformas).86–88 The risk categories are different
from those for the other oncology drugs as they are based on the 10-year risk of events.
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Several studies have shown that, particularly for prostate cancer patients who have a mean
age >60 years and frequently have concomitant coronary artery disease, that GnRH agonists
given as ADT increase CV risk and mortality, and preventative strategies are needed.89
Whilst these CV risk calculators were not specifically developed for cancer patients
receiving GnRH agonists or other ADT, and frequently excluded patients with active cancer,
they are established from large population studies and included in the ESC guidelines for
CVD prevention and are also included in many national cardiology society guidelines. The
Lyon et al. Page 7
risk calculators collect various parameters associated with future risk of atherosclerosis-
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related CVD, although the specific parameters required vary between the different risk
calculators (online supplementary Table S1). It was the consensus of the authors to
recommend the use of these established CV risk calculators specifically for patients
receiving ADT including GnRH agonists for prostate cancer which have an increased risk of
MI and stroke. The coronary heart disease risk level can then be calculated using the online
web-based calculator for the risk score as follows:
• <10% 10-year risk = low risk level
• 10–19% 10-year risk = medium risk level
• ≥20% 10-year risk = high risk level
The result should be communicated to the patient and to the appropriate healthcare
professionals (primary care physician, cardiologist, cardio-oncologist) to address modifiable
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CV risk factors according to ESC guidelines for CVD prevention.86 These are primary
prevention CV risk calculators and are only suitable for cancer patients scheduled to receive
ADT who have not previously presented with the clinical manifestations of atherosclerotic
disease. Any prostate cancer patient with a previous history of CVD is high risk and should
be evaluated by an appropriate healthcare professional to review their symptom status and
CV risk factor control. These CV risk calculators are not suitable for other cardiotoxic
cancer therapies where there is an increased risk of HF, hypertension, QT prolongation and
other CVDs. In addition, data on the increased CV risk in women receiving GnRH agonists
for breast or ovarian cancer are lacking and therefore this proforma is currently only
applicable to men with prostate cancer scheduled to receive a GnRH agonist.
We recommend completion of the baseline CV risk assessment proformas in all patients

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scheduled to receive one of the seven oncology drug classes with potential cardiotoxicity
listed in Table 1. This can be performed after the decision has been made by the treating
oncologist or haematologist to start a potentially cardiotoxic cancer treatment. It is important
to emphasise that this needs to be completed promptly so that cancer treatment is not
delayed and can be commenced safely. In emergency scenarios, guideline-based cancer
treatment should be commenced and the baseline CV risk assessment proformas can be
completed once clinical stability has been achieved (e.g. CML presenting with blast crisis,
solid tumours presenting with acute oncological emergencies).
Following completion of the baseline CV risk assessment proformas the risk level should be
recorded in the patient’s medical records, reviewed by the treating oncologist or haemato-
oncologist and communicated to the patient and their primary care physician. The specific
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treatment pathways for each of the drug categories and risk levels is beyond the scope of this
position statement and will be addressed in a future HFA position statement, but the authors
recommend, conceptually, the following general principles until more detailed guidance is
available:
• Low risk level cancer patients continue with treatment with CV surveillance as
appropriate according to local, national and international guidelines.
Lyon et al. Page 8
• Medium risk cancer patients require closer monitoring of CV health during

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treatment or consideration for referral for a cardio-oncology or cardiology

assessment.
• High and very high risk level patients are referred for a cardio-oncology or
cardiology assessment, ideally in a specialist cardio-oncology service (if
available) to optimise management of their pre-existing CVD and modifiable CV
risk factors, and provide a personalised management plan for surveillance during
cancer treatment.
It is important that pathways exist to minimise the time delay from risk assessment and
referral to cardiology clinical assessment, and the decision and management plan are
communicated to the referring oncology or haemato-oncology team promptly to prevent any
delay in starting cancer treatment, following the core principles of a cardio-oncology
service.2 The timing and nature of CV surveillance recommendations will depend upon
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various factors including the cardiotoxicity profile of the cancer therapy required (Table 1),
the risk factors contributing to the risk level calculation and patient preference. CV imaging
and cardiac biomarkers are available for surveillance and detection of early cardiotoxicity,
and their role in cancer patients receiving potentially cardiotoxic cancer therapies and
surveillance algorithms are the topic of two HFA position statements (in preparation).
We recommend that following implementation of these risk proformas, which could be

digital or paper-based depending upon local medical records, an audit and review of the risk
stratification process is performed to identify the frequency of application, percentage of risk
assessments completed, the actions taken from the assessment and how that conforms to
local pathways and standards of care. Oncologists and haemato-oncologists should identify
cardiologists with whom to collaborate in setting up pathways of care for their high risk and
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very high risk patients. If cardiology support is not available locally, then whilst identifying
regional or national options these risk proformas should provide a guide for oncologists to
consider alternative, non-cardiotoxic cancer therapies in patients identified as high risk or
very high risk where alternative treatment options are available. In the long term collection
of outcome data, and comparison to retrospective datasets regarding CV events, could be
considered. We suggest collaborative studies between centres implementing these risk
stratification proformas to assess their impact in reducing CV complications of cancer
therapies as well as changes in the overall cancer and CV outcomes. Large datasets can also
serve to refine the weighting of risk for the different parameters for each cancer drug class,
with the ultimate aim to improve the sensitivity and predictive value.
Conclusions and future directions

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Cardiology and oncology professional society guidelines and expert position statements on
CVD in cancer patients uniformly recommend baseline CV risk assessment for oncology
patients scheduled to receive potentially cardiotoxic cancer therapies.1,4–6 Here we present
proformas for baseline CV risk assessment which can be employed by oncology and
haemato-oncology services for patients scheduled to receive one of seven cardiotoxic cancer
therapies. Assessment of baseline CV risk is part of a personalised approach to care for
cancer patients. The identification of cancer patients who are at an increased risk of CV
Lyon et al. Page 9
complications in a timely manner is important so that appropriate measures can be

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implemented to eliminate or at least mitigate their CV risk and ensure, where possible, that
cancer patients receive their treatment safely. There is the potential for these proformas to be
electronic with semi-automated population of the fields from the electronic patient record if
a suitable platform exists. Future studies are required to validate and refine these proformas,
including the specific weighting of each risk factor and the addition of new risk factors as
they are identified. The impact of proformas upon overall survival and both CV-related and
cancer-related outcomes and mortality needs to be assessed as well. The long-term goal is to
improve both oncology and CV outcomes for this patient population through a personalised
approach to CV risk, which should allow cancer patients to complete their evidence-based
cancer treatments free from CV toxicity and CVD, leading to an improvement in overall
survival.
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Supplementary Material
Refer to Web version on PubMed Central for supplementary material.
Authors
Alexander R. Lyon1,*, Susan Dent2, Susannah Stanway3, Helena Earl4, Christine
Brezden-Masley5, Alain Cohen-Solal6, Carlo G. Tocchetti7, Javid J. Moslehi8, John
D. Groarke9, Jutta Bergler-Klein10, Vincent Khoo11,12, Li Ling Tan13, Markus S.
Anker14, Stephan von Haehling15,16, Christoph Maack17, Radek Pudil18, Ana
Barac19, Paaladinesh Thavendiranathan20, Bonnie Ky21, Tomas G. Neilan22, Yury
Belenkov23, Stuart D. Rosen1, Zaza Iakobishvili24, Aaron L. Sverdlov25, Ludhmila A.
Hajjar26, Ariane V.S. Macedo27, Charlotte Manisty28, Fortunato Ciardiello29,
Dimitrios Farmakis30,31, Rudolf A. de Boer32, Hadi Skouri33, Thomas M. Suter34,
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Daniela Cardinale35, Ronald M. Witteles36, Michael G. Fradley21, Joerg

Herrmann37, Robert F. Cornell38, Ashutosh Wechelaker39, Michael J. Mauro40,
Dragana Milojkovic41, Hugues de Lavallade42, Frank Ruschitzka43, Andrew J.S.
Coats44,45, Petar M. Seferovic46, Ovidiu Chioncel47,48, Thomas Thum49, Johann
Bauersachs50, M. Sol Andres1, David J. Wright51, Teresa López-Fernández52, Chris
Plummer53, Daniel Lenihan54
Affiliations
1Cardio-Oncology Service, Royal Brompton Hospital and Imperial College, London,
UK 2Duke Cancer Institute, Duke University, Durham, NC, USA 3Breast Unit, Royal
Marsden Hospital, Surrey, UK 4Department of Oncology, University of Cambridge
and NIHR Cambridge Biomedical Research Centre, Cambridge, UK 5Division of
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Medical Oncology, Sinai Health System, Mount Sinai Hospital, Toronto, Canada
6UMR-S 942, Paris University, Cardiology Department, Lariboisiere Hospital, AP-HP,
Paris, France 7Department of Translational Medical Sciences and Interdepartmental

Center for Clinical and Translational Research (CIRCET), Federico II University,
Naples, Italy 8Cardio-Oncology Program, Department of Medicine, Vanderbilt
University Medical Center, Nashville, TN, USA 9Cardio-Oncology Program, Brigham
& Women’s Hospital, Harvard Medical School, Boston, MA, USA 10Department of
Lyon et al. Page 10
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Cardiology, Medical University of Vienna, Vienna, Austria 11Department of Clinical

Oncology, Royal Marsden Hospital and Institute of Cancer Research, London, UK
12Department of Medical Imaging and Radiation Sciences, Monash University and
Department of Medicine, Melbourne University, Melbourne, Australia 13Department

of Cardiology, National University Heart Centre, Singapore, National University
Health System, Singapore, Singapore 14Division of Cardiology and Metabolism,
Department of Cardiology, Charité and Berlin Institute of Health Center for
Regenerative Therapies (BCRT) and DZHK (German Centre for Cardiovascular
Research), partner site Berlin and Department of Cardiology, Charité Campus
Benjamin Franklin, Berlin, Germany 15Department of Cardiology and Pneumology,
University of Goettingen Medical Center, Goettingen, Germany 16German Center for
Cardiovascular Research (DZHK), partner site Goettingen, Goettingen, Germany
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17Comprehensive Heart Failure Center, University Clinic Würzburg, Würzburg,
Germany 18First Department of Medicine – Cardioangiology, Charles University

Prague, Medical Faculty and University Hospital Hradec Kralove, Prague, Czech
Republic 19MedStar Heart and Vascular Institute, Georgetown University,
Washington, DC, USA 20Ted Rogers Program in Cardiotoxicity Prevention and Joint
Division of Medical Imaging, Peter Munk Cardiac Center, Toronto General Hospital,
University Health Network, University of Toronto, Toronto, Canada 21University of
Pennsylvania, Philadelphia, PA, USA 22Cardio-Oncology Program, Division of
Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard
Medical School, Boston, MA, USA 23Sechenov Medical University, Moscow, Russia
24Department of Community Cardiology, Tel Aviv Jaffa District, Clalit Health Fund
and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 25School of
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Medicine and Public Health, University of Newcastle and “Cancer and the Heart”
Program, Hunter New England LHD, Newcastle, Australia 26Cardio-Oncology,
Department of Cardio-Pneumology, University of São Paulo, São Paulo, Brazil
27Santa Cardio-Oncology, Santa Casa de São Paulo and Rede Dor São Luiz, São
Paulo, Brazil 28Barts Heart Centre and University College London, London, UK
29Department of Precision Medicine, Luigi Vanvitelli University of Campania, Naples,
Italy 30University of Cyprus Medical School, Nicosia, Cyprus 31Cardio-Oncology

Clinic, Heart Failure Unit, “Attikon” University Hospital, National and Kapodistrian
University of Athens Medical School, Athens, Greece 32Department of Cardiology,
University of Groningen, University Medical Center Groningen, Groningen, The
Netherlands 33Cardiology Division, Internal Medicine Department, American
University of Beirut Medical Center, Beirut, Lebanon 34Department of Cardiology,
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Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland

35Cardioncology Unit, European Institute of Oncology, IRCCS, Milan, Italy 36Stanford
University School of Medicine, Stanford, CA, USA 37Department of Cardiovascular

Diseases, Mayo Clinic, Rochester, MN, USA 38Vanderbilt University Medical Center,
Nashville, TN, USA 39National Amyloidosis Centre, University College London,
London, UK 40Memorial Sloan Kettering Cancer Center, New York, NY, USA
41Department of Haematology, Hammersmith Hospital, Imperial College, London,
UK 42Department of Haematological Medicine, King’s College Hospital, London, UK
Lyon et al. Page 11
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43University Heart Center, Department of Cardiology, University Hospital Zurich,

Zurich, Switzerland 44University of Warwick, Warwick, UK 45Pharmacology, Centre
of Clinical and Experimental Medicine, IRCCS San Raffaele Pisana, Rome, Italy
46Faculty of Medicine and Serbian Academy of Sciences and Arts, University of
Belgrade, Belgrade, Serbia 47Emergency Institute for Cardiovascular Diseases ‘Prof.

C.C. Iliescu’, Bucharest, Romania 48University of Medicine Carol Davila, Bucharest,
Romania 49Institute of Molecular and Translational Therapeutic Strategies,
Hannover Medical School, Hannover, Germany 50Department of Cardiology and
Angiology, Hannover Medical School, Hannover, Germany 51Liverpool Centre for
Cardiovascular Science, Liverpool Heart and Chest Hospital, Liverpool, UK
52Cardiology Service, Cardio-Oncology Unit, La Paz University Hospital and IdiPAz
Research Institute, Ciber CV, Madrid, Spain 53Department of Cardiology, The

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Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University,
Newcastle, UK 54Cardio-Oncology Center of Excellence, Washington University in
St Louis, St Louis, MO, USA
Acknowledgments
Funding
A.R.L. is supported by the Fondation Leducq Network of Excellence in Cardio-Oncology. C.G.T. is supported by
the grant ‘Ricerca di Ateneo Federico II 2017’. A.L.S. is supported by the Heart Foundation of Australia Future
Leader Fellowship (Award ID 101918). J.M. is supported by R01 HL141466. R.A.d.B. is supported by the
European Research Council (ERC CoG 818715, SECRETE-HF), and furthermore by the Netherlands Heart
Foundation (CVON DOSIS, grant 2014–40, CVON SHE-PREDICTS-HF, grant 2017–21; CVON RED-CVD, grant
2017–11; and CVON PREDICT2, grant 2018–30); and the Innovational Research Incentives Scheme program of
the Netherlands Organization for Scientific Research (NWO VIDI, grant 917.13.350). C.M. is supported by the
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German Research Foundation (DFG; SFB-894, TRR-219; Ma 2528/7–1) and the German Ministry of Education
and Research (BMBF; 01EO1504). M.S.A. has received research support from the German Cardiovascular
Research Center.
Conflict of interest: A.R.L. has 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. S.D. has received speaker, advisory board or research
funding from Novartis, Eli Lilly, Genetech and Pfizer. S.S. has received speaker, advisory board or consultancy fees
from Roche, Clinigen and Eli Lilly. H.E. has received grants from Roche and Sanofi-Aventis, and advisory board or
speaker fees from Daiichi-Sankyo, AstraZeneca, INTAS Pharmaceuticals, Pfizer, Amgen and Prime Oncology.
A.C.S. has received speaker, advisory board or consultancy fees and/or research grants from Novartis, Servier,
Amgen, Abbott, Vifor, AstraZeneca, MSD, Roche, Takeda and Bristol-Myers Squibb. J.M. has served as a
consultant for Novartis, Pfizer, Bristol-Myers Squibb, Takeda, Pharmacyclics, Regeneron, Myokardia, Audentes
Pharmaceuticals, AstraZeneca, Deciphera, Ipsen, and Intrexon and has received grant funding from Pfizer and
Bristol-Myers Squibb. J.D.G. receives research funding from Amgen. T.G.N. has received speaker, advisory board
or consultancy fees from Parexel, Intrinsic Imaging, Bristol-Myers Squibb, H3 Biomedicine, Aprea Therapeutics.
A.L.S. has received speaker fees, advisory board and/or research grants from Bayer, Biotronik, Novartis and Vifor.
B.K. has received consultancy fees from Bristol-Myers Squibb. C.G.T. received speaking fees from Alere. H.S.
Author Manuscript
received honoraria for presentations from Servier, Novartis, AstraZeneca, Abbott and Boehringer Ingelheim. C.M.
has received speak fees from Pfizer. R.F.C. has received advisory board or consultancy fees from Karyopharm
Therapeutics, Takeda and Janssen. V.K. has participated in advisory boards, conferences and educational meetings
for Accuray, Astellas, Bayer, Janssen and Boston Scientific. T.L.F. has received speaker fees from Janssen, Amgen,
Servier, Daiichi-Sankyo, MSD, and Philips. A.B. serves on DSMB for CTI Biopharma and has received honoraria
from Bristol-Myers Squibb. P.T. has received speaker fees from Boehringer Ingelheim, Takeda, Amgen. M.S.A. has
received personal fees from Servier. D.F. has received consultation fees, speaker honoraria and/or travel grants from
Abbott, Boehringer Ingelheim, Daiichi-Sankyo, Menarini, Novartis, Pfizer, Roche and Servier. C.M. has received
speaker, advisory board or consultancy fees from Servier, Amgen, Boehringer Ingelheim, Astra, Novartis, Bayer,
Berlin Chemie, Bristol-Myers Squibb, Daiichi-Sankyo, Pfizer. S.D.R. has received speaker and advisory board
consultancy fees from Servier, Novartis and Clinigen Group. M.G.F. has received advisory board fees from Novartis
Lyon et al. Page 12
and research funding from Medtronic. Z.I. has received advisory board or speaker fees from Novartis, AstraZeneca,
Boehringer Ingelheim, Pfizer, Bayer, Eli Lilly. T.T. is founder and shareholder of Cardior Pharmaceuticals, served
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in an advisory board of Novo Nordisk and received honoraria from Amicus Therapeutics and Sanofi-Genzyme. J.B.
has received speaker, advisory board or consultancy fees and/or research grants from Novartis, Vifor, Bayer,
Servier, Abiomed, Boehringer Ingelheim, Daiichi-Sankyo, AstraZeneca, CVRx, BMS, Pfizer, MSD, Abbott,
Medtronic and Zoll not related to this manuscript. C.P. has received travel expenses and honoraria for speaking at
educational meetings or advisory boards from Amgen, Bayer, Celgene, Ferring, Incyte, Novartis, Pfizer and Roche.
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Lyon et al. Page 19
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Figure 1.
Examples of five different patients and primary or secondary prevention based on the history
of pre-existing cardiovascular (CV) disease and/or prior cardiotoxicity from treatment of a
previous malignancy.
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Lyon et al. Page 20
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Figure 2.
The different risk factors which contribute to baseline cardiovascular (CV) risk in a cancer
patient scheduled to receive a cardiotoxic cancer treatment, and a checklist of the clinical
history and investigations required at baseline prior to starting a cardiotoxic cancer therapy.
*Cardiac biomarkers (troponin and natriuretic peptides) should be measured where
available. BNP, brain natriuretic peptide; ECG, electrocardiogram; HbA1c, glycated
haemoglobin; NT-proBNP, N-terminal pro-brain natriuretic peptide.
Author Manuscript
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Table 1
Cancer therapy classes identified for cardiovascular baseline risk assessment and associated cardiovascular toxicity
Cancer treatment class Cancer indication Treatment-related CV toxicity

Lyon et al.
Anthracycline chemotherapy Breast cancer, lymphoma, acute leukaemia, sarcoma Heart failure
(doxorubicin, epirubicin, daunorubicin, idarubicin) Asymptomatic LVSD
Atrial and ventricular arrhythmias
HER2-targeted therapies HER2+ breast cancer Heart failure
(trastuzumab, pertuzumab, trastuzumab emtansine (T-DM1), lapatinib, HER2+ gastric cancer Asymptomatic LVSD
neratinib, tucatinib)
Hypertension
VEGF inhibitors VEGF TKIs: renal cancer, hepatocellular cancer, thyroid cancer, colon Hypertension
cancer, sarcoma, GIST
TKIs (sunitinib, pazopanib, sorafenib, axitinib, tivozanib, cabozantinib, Heart failure
regorafenib, lenvatinib, vandetinib) and antibodies (bevacizumab,
ramucirumab) Asymptomatic LVSD
Antibodies: breast cancer, ovarian cancer, gastric cancer, gastro- Myocardial ischaemia and infarction
oesophageal cancer, colon cancer
QTc prolongation
Multi-targeted kinase inhibitors: Chronic myeloid leukaemia Arterial thrombosis
second and third generation BCR-ABL TKIs a
(myocardial infarction, stroke and PAOD )
Venous thromboembolism
(ponatinib, nilotinib, dasatinib, bosutinib) Hypertension
Heart failure and asymptomatic LVSD
b
Atherosclerosis
b
QTc prolongation
c
Pulmonary hypertension
Proteasome inhibitors Multiple myeloma d
Heart failure
(carfilzomib, bortezomib, ixazomib) d
Asymptomatic LVSD
Immunomodulatory drugs Myocardial ischaemia and infarction
(lenalidomide, pomalidomide) Atrial and ventricular arrhythmias
Venous thromboembolism
Arterial thrombosis
Hypertension
Page 21
Cancer treatment class Cancer indication Treatment-related CV toxicity
Combination RAF and MEK inhibitors Raf mutant melanoma Heart failure and asymptomatic LVSD
(dabrafenib + trametinib, vemurafenib + cobimetinib, encorafenib + Hypertension
binimetinib)
Lyon et al.
e
QTc prolongation
Androgen deprivation therapies Prostate cancer Atherosclerosis
GnRH agonists (goserelin, leuprorelin) f Myocardial ischaemia and infarction
ER+ breast cancer
Antiandrogrens (abiraterone) Diabetes mellitus
Hypertension
Immune checkpoint inhibitors: Melanoma (metastatic and adjuvant) Myocarditis including fulminant myocarditis
anti-programmed cell death 1 inhibitors (nivolumab, pembrolizumab) Metastatic renal cancer, non-small cell lung cancer, small cell lung cancer, Pericarditis
refractory Hodgkin’s lymphoma, metastatic triple negative breast cancer,
metastatic urothelial cancer, liver cancer, MMR-deficient cancer Non-inflammatory heart failure
anti-cytotoxic T-lymphocyte-associated protein 4 inhibitor Ventricular arrhythmias
(ipilimumab)
AV block
anti-programmed death-ligand 1 inhibitors (avelumab, atezolizumab, Acute coronary syndromes including
durvalumab) atherosclerotic plaque rupture and vasculitis
AV, atrio-ventricular; CV, cardiovascular; ER, oestrogen receptor; GIST, gastro-intestinal stromal tumour; GnRH, gonadotropin release hormone; LVSD, left ventricular systolic dysfunction; MMR,
mismatch repair; PAOD, peripheral arterial occlusive disease; TKI, tyrosine kinase inhibitor; VEGF, vascular endothelial growth factor.
a
Associated with ponatinib.
b
Associated with ponatinib and nilotinib.
c
Associated with dasatinib.
d
Associated with carfilzomib.
e
Associated with vemurafenib and cobimetinib.
f
The risk scores for androgen deprivation therapies in this position statement relate to androgen deprivation therapies for prostate cancer only.
Page 22
Table 2
Baseline cardiovascular risk stratification proforma for anthracycline chemotherapy
Risk factor Score Level of evidence References

Lyon et al.
Previous cardiovascular disease

Heart failure or cardiomyopathy Very high B 10,11
Severe valvular heart disease High C 11
Myocardial infarction or previous coronary revascularisation (PCI or CABG) High C 10–12
Stable angina High C 10–12
Baseline LVEF <50% High B 10
Borderline LVEF 50–54% Medium2 C
Cardiac biomarkers (where available)
a Medium1 C 13–15
Elevated baseline troponin
a Medium1 C 16,17
Elevated baseline BNP or NT-proBNP
Demographic and cardiovascular risk factors
Age ≥80 years High B 10,12,18
Age 65–79 years Medium2 B 10,18–20
b Medium1 B 11,12,21
Hypertension
c Medium1 C 10–12
Diabetes mellitus
d Medium1 C
Chronic kidney disease
Previous cardiotoxic cancer treatment
Previous anthracycline exposure High B 18–20,22–25
Prior radiotherapy to left chest or mediastinum High C 20,22,23,26,27
Previous non-anthracycline-based chemotherapy Medium1 C 24,25,28
Lifestyle risk factors
Current smoker or significant smoking history Medium1 C 23
Obesity (BMI >30 kg/m2) Medium1 C 20,29,30

Risk level
BMI, body mass index; BNP, brain natriuretic peptide; CABG, coronary artery bypass graft; LVEF, left ventricular ejection fraction; NT-proBNP, N-terminal pro-brain natriuretic peptide; PCI, percutaneous
coronary intervention.
Page 23
Low risk = no risk factor OR one medium1 risk factor; Medium risk = medium risk factors with a total of 2–4 points; High risk = medium risk factors with a total of ≥5 points OR any high risk factor; Very
high risk = any very high risk factor.
a
Elevated above the upper limit of normal for local laboratory reference range.
b
Systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg, or on treatment.
c
Lyon et al.
Glycated haemoglobin >7.0% or >53 mmol/mol, or on treatment.

d
Estimated glomerular filtration rate <60 mL/min/1.73 m2.
Please see online supplementary Table S2 for the 1 page printable version for clinical use.
Page 24
Table 3
Baseline cardiovascular risk stratification proforma for HER2-targeted cancer therapies (trastuzumab, pertuzumab, T-DM1, lapatinib, neratinib)

Lyon et al.

Heart failure or cardiomyopathy Very high C 31
Myocardial infarction or CABG High B 31,32
Stable angina High B 31–34
Severe valvular heart disease High C 31
Baseline LVEF <50% High C
Borderline LVEF 50–54% Medium2 B 35–37
a Medium2 C 31,32
Arrhythmia
b Medium2 B 38,39
b Medium2 C 17
Age ≥80 years High B 32,33
Age 65–79 years Medium2 B 35,36,40,41
c Medium1 B 32–36,42,43
Hypertension
d Medium1 C 31,32,42
Diabetes mellitus
e Medium1 C 32
Current cancer treatment regimen
Includes anthracycline before HER2-targeted therapy f B 32,40,41,43–45
Medium1
Prior trastuzumab cardiotoxicity Very high C
g Medium2 B 42
Prior (remote) anthracycline exposure
Prior radiotherapy to left chest or mediastinum Medium2 C 41,46,47
Page 25
Obesity (BMI >30 kg/m2) Medium1 C 29,34,43,45

Risk level
Lyon et al.
BMI, body mass index; BNP, brain natriuretic peptide; CABG, coronary artery bypass graft; LVEF, left ventricular ejection fraction; NT-proBNP, N-terminal pro-brain natriuretic peptide.
a
Atrial fibrillation, atrial flutter, ventricular tachycardia, or ventricular fibrillation.
b
c
d
e
f
High risk if anthracycline chemotherapy and trastuzumab delivered concurrently.
g
Previous malignancy (not current treatment protocol).
Page 26
Table 4
Baseline cardiovascular risk stratification proforma for vascular endothelial growth factor inhibitors

Lyon et al.

Heart failure or cardiomyopathy Very high C 48–50
Arterial vascular disease (IHD, PCI, CABG, stable angina, TIA, stroke, PVD) Very high C 50–52
Venous thrombosis (DVT or PE) High C
QTc ≥480 ms High C
450 ms ≤ QTc <480 ms (men) 460 ms ≤ QTc <480 ms (women) Medium2 C
a Medium2 C 50
Arrhythmia
b Medium1 C 50
b Medium1 C 53
Age ≥75 years High C 54–56
Age 65–74 years Medium1 C 48,54,56
c High C 48,50–52,54,55
Hypertension
d Medium1 C 50
Diabetes mellitus
C 49,50
e Medium1
Hyperlipidaemia
f Medium1 C 57
Proteinuria Medium1 C
Prior anthracycline exposure High C
Prior radiotherapy to left chest or mediastinum Medium1 C
Page 27
Obesity (BMI >30 kg/m2) Medium1 C 50,54,58

Risk level
Lyon et al.
BMI, body mass index; BNP, brain natriuretic peptide; CABG, coronary artery bypass graft; DVT, deep vein thrombosis; IHD, ischaemic heart disease; LVEF, left ventricular ejection fraction; NT-proBNP,
N-terminal pro-brain natriuretic peptide; PCI, percutaneous coronary intervention; PE, pulmonary embolism; PVD, peripheral vascular disease; TIA, transient ischaemic attack.
a
b
c
d
e
Non-high-density lipoprotein cholesterol level >3.8 mmol/L (>145 mg/dL).
f
Page 28
Table 5
Baseline cardiovascular risk stratification proforma for multi-targeted kinase inhibitors for chronic myeloid leukaemia including second and third
generation BCR-ABL tyrosine kinase inhibitors
Lyon et al.

Arterial vascular disease (IHD, PCI, CABG, stable angina, TIA, stroke, PVD) Very high C 59,60
Arterial thrombosis with TKI Very high C
Heart failure or LVSD High C
BCR-ABL TKI-mediated LVSD High C
f High C
Abnormal ABPI
g High C
Pulmonary arterial hypertension
Venous thromboembolism (DVT/PE) Medium2 C 60,61
a Medium2 C
Arrhythmia
QTc ≥ 480 ms High C
450 ms ≤ QTc < 480 ms (men) 460 ms ≤ QTc < 480 ms (women) Medium2 C
Demographic and other cardiovascular risk factors
Cardiovascular disease 10-year risk score >20% High B 62
b Medium2 B 59–61
Hypertension
c Medium1 B 63
Diabetes
d Medium1 B 60,61
Hyperlipidaemia
Age ≥75 years High C
Age 65–74 years Medium2 B 61
Age ≥60 years Medium1 B 61
e Medium1 C
Family history of thrombophilia Medium1 C
Lifestyle and other factors
Current smoker or significant smoking history High B 60
Obesity (BMI >30kg/m2) Medium1 C
Page 29
Risk level
ABPI, ankle–brachial pressure index; BMI, body mass index; CABG, coronary artery bypass graft; DVT, deep vein thrombosis; IHD, ischaemic heart disease; LVEF, left ventricular ejection fraction; LVSD,
Lyon et al.
left ventricular systolic dysfunction; PCI, percutaneous coronary intervention; PCI, percutaneous coronary intervention; PE, pulmonary embolism; PVD, peripheral vascular disease; TIA, transient
ischaemic attack; TKI, tyrosine kinase inhibitor.
a
b
c
d
Non-high-density lipoprotein cholesterol level >3.8mmol/L (>145mg/dL).
e
Estimated glomerular filtration rate <60mL/min/1.73 m2.
f
ABPI ≤0.9.
g
Peak systolic pulmonary artery pressure at rest ≥35 mmHg when estimated non-invasively on echocardiography.
Page 30
Table 6
Baseline cardiovascular risk stratification proforma for proteasome inhibitors and immunomodulatory agents for multiple myeloma

Lyon et al.

Heart failure or cardiomyopathy Very high C 64
Prior proteasome inhibitor cardiotoxicity Very high C
Venous thrombosis (DVT or PE) Very high C 64
Cardiac amyloidosis Very high C
Arterial vascular disease (IHD, PCI, CABG, stable angina, TIA, stroke, PVD) Very high C 64
Prior immunomodulatory drug CV toxicity High B 65
a Medium2 C 64
Arrhythmia
b Medium1 C
Left ventricular hypertrophy
c Medium2 C
c High B 66
Age ≥75 years High C
Age 65–74 years Medium1 C
d Medium1 C 64,67
Hypertension
e Medium1 C
Diabetes mellitus
f Medium1 C 64
Hyperlipidaemia
g Medium1 C
Family history of thrombophilia Medium1 C
Prior anthracycline exposure High C 68
Prior thoracic spine radiotherapy Medium1 C 68
Page 31
Current myeloma treatment

High-dose dexamethasone >160 mg/month Medium1 C
Lyon et al.

Obesity (BMI >30 kg/m2) Medium1 C

Risk level
BMI, body mass index; BNP, brain natriuretic peptide; CABG, coronary artery bypass graft; DVT, deep vein thrombosis; IHD, Ischaemic heart disease; LVEF, left ventricular ejection fraction; NT-proBNP,
N-terminal pro-brain natriuretic peptide; PCI, percutaneous coronary intervention; PE, pulmonary embolism; PVD, peripheral vascular disease; TIA, transient ischaemic attack.
a
b
Left ventricular wall thickness >1.2 cm.
c
d
e
Glycated haemoglobin >7.0% or >53 mmol/mol or on treatment.
f
Non-high-density liporotein cholesterol level >3.8mmol/L (>145mg/dL).
g
Estimated glomerular filtration rate <60mL/min/1.73 m2.
Page 32
Table 7
Baseline cardiovascular risk stratification proforma for combination RAF and MEK inhibitors (dabrafenib + trametinib, vemurafenib + cobimetinib,
encorafenib + binimetinib)
Lyon et al.
Risk factor Score Level of evidence

Heart failure or cardiomyopathy Very high C
Myocardial infarction or CABG High C
Stable angina High C
Severe valvular heart disease High C
a Medium1 C
Arrhythmia
b Medium2 C
b Medium2 C
Age ≥65 years Medium1 C
c Medium2 C
Hypertension
d Medium1 C
Diabetes mellitus
e Medium1 C
f High C
Prior anthracycline exposure
Prior radiotherapy to left chest or mediastinum Medium2 C
Current smoker or significant smoking history Medium1 C
Obesity (BMI >30 kg/m2) Medium1 C

Risk level
BMI, body mass index; BNP, brain natriuretic peptide; CABG, coronary artery bypass graft; LVEF, left ventricular ejection fraction; NT-proBNP, N-terminal pro-brain natriuretic peptide.
Page 33
a
b
c
d
Lyon et al.
e
f
Previous malignancy.
Page 34
Lyon et al. Page 35
Table 8
Baseline cardiovascular risk stratification proforma for androgen deprivation therapies including
Author Manuscript
gonadotrophin-releasing hormone agonists (goserelin, leuprolide) and anti-androgen therapies (abiraterone)

for prostate cancer
a Score
Clinical risk score
b High
Known pre-existing cardiovascular disease (CVD) or CVD 10-year risk score ≥20%
CVD 10-year risk score ≥10% to <20% Medium
CVD 10-year risk score <10% Low
CVD, cardiovascular disease.
Risk factors and variables required: age, gender, ethnic group, height, weight, social class indicator (Townsend quintile), smoking status (current,
ex- or non-smoker), total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure (mmHg), diabetes status (yes/no), family history
of premature CVD (before 60 years) (yes/no), chronic kidney disease (yes/no), atrial fibrillation (yes/no), systemic inflammatory disease (e.g.
rheumatoid arthritis, psoriasis) (yes/no).
Author Manuscript
a
For validated CVD risk scores, see Table 9.
b
Prior symptomatic coronary artery disease, carotid artery disease or peripheral artery disease, e.g. stable angina, acute myocardial infarction,
transient ischaemic attack/stroke, ischaemic claudication.
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Lyon et al. Page 36
Table 9
Atherosclerosis-related cardiovascular risk calculators

Author Manuscript
Risk score Website
ESC HeartScore www.heartscore.org

QRISK®3 https://qrisk.org/three
JBS3 risk score (2014) http://www.jbs3risk.com
ACC/AHA pooled cohort CV risk calculator (2013) http://www.cvriskcalculator.com
ACC, American College of Cardiology; AHA, American Heart Association; ESC, European Society of Cardiology; JBS, Joint British Societies.
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Author Manuscript
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Baseline cardiovascular risk assessment in cancer patients

targeted molecular therapies, in addition to the continued use of anthracycline chemotherapy,

a multidisciplinary cardio-oncology approach is to support best practice, guideline-directed

assessment tool to facilitate CV risk stratification in oncology and haemato-oncology

• Risk is a continuous variable.

• Evidence or expert consensus exists that a parameter contributes to future risk of

• Cancer patients identified at increased risk of cancer treatment-related CV

• Baseline CV risk stratification should be completed promptly and should not

• Decisions to withhold effective but potentially cardiotoxic cancer treatments in

• Decisions regarding switching to alternative less cardiotoxic cancer treatments in

• Cardiovascular treatment interventions should be considered to mitigate CV risk

existing CVD and modifiable CV risk factors reviewed and optimised by a

suitable healthcare professional (e.g. cardio-oncology service, cardiologist or

• Baseline CV risk assessment proformas should be easy to understand and

• The application and impact of baseline CV risk assessment proformas can be

Design and application of baseline cardiovascular risk proformas

• Anthracycline chemotherapy: the main CV complications of anthracycline

• HER2 targeted therapies: the main CV complications of HER2 targeted therapies

many act via multi-targeted inhibition of tyrosine kinases]: the main CV

• Multi-targeted kinase inhibitors for chronic myeloid leukaemia (CML) targeting

(ponatinib), venous thromboembolism, systemic hypertension, LVD and HF,

accelerated atherosclerosis (ponatinib and nilotinib), QTc prolongation

• Proteasome inhibitors (PIs) and immunomodulatory drugs (IMIDs): the main CV

• Combination RAF and MEK inhibitor treatment: the main CV complications of

• Androgen deprivation therapies (ADT) for prostate cancer treatment including

gonadotropin release hormone (GnRH) agonists: ADT are associated with an

• Immune checkpoint inhibitors: myocarditis including fulminant myocarditis,

• Column 1 lists the CV risk factors

• Column 2 is the box to complete if present (yes/no)

The conceptual background of these recommendations is that both patient-related as well as

• Elevated circulating cardiac biomarkers pre-treatment (if measured)

• Demographic and co-existing medical conditions recognised as CV risk factors

• Previous cardiotoxic cancer treatment

• Lifestyle-related CV risk factors.

1. Patients with no risk factors are ‘low risk’

3. Medium risk factors are given a point weighting as medium1 or medium2

• Patients with several medium risk factors with points totalling 5 or

• <10% 10-year risk = low risk level

• 10–19% 10-year risk = medium risk level

• ≥20% 10-year risk = high risk level

We recommend completion of the baseline CV risk assessment proformas in all patients

• Medium risk cancer patients require closer monitoring of CV health during

treatment or consideration for referral for a cardio-oncology or cardiology

We recommend that following implementation of these risk proformas, which could be

Conclusions and future directions

complications in a timely manner is important so that appropriate measures can be

Daniela Cardinale35, Ronald M. Witteles36, Michael G. Fradley21, Joerg

Paris, France 7Department of Translational Medical Sciences and Interdepartmental

Cardiology, Medical University of Vienna, Vienna, Austria 11Department of Clinical

Department of Medicine, Melbourne University, Melbourne, Australia 13Department

17Comprehensive Heart Failure Center, University Clinic Würzburg, Würzburg,

Germany 18First Department of Medicine – Cardioangiology, Charles University

Italy 30University of Cyprus Medical School, Nicosia, Cyprus 31Cardio-Oncology

Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland

University School of Medicine, Stanford, CA, USA 37Department of Cardiovascular

UK 42Department of Haematological Medicine, King’s College Hospital, London, UK

43University Heart Center, Department of Cardiology, University Hospital Zurich,

Belgrade, Belgrade, Serbia 47Emergency Institute for Cardiovascular Diseases ‘Prof.