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What is the problem

Cancer patients are a high cardiovascular risk cohort. Both cancer and cardiovascular disease have interlinked risk factors in common such as increasing age, obesity and smoking. Many oncological therapies also have associated cardiovascular side effects which further increase the cardiovascular risk profile of cancer patients.

Cancer therapy related cardiovascular toxicity (CTR-CVT) refers to any cancer treatment related effects that cause injury to the cardiovascular system. This injury can lead to both structural and/or functional injury to the myocardium.

Commonly encountered oncological therapies which cause cardiotoxicity

High dose chest radiotherapy
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Anthracyclines e.g. doxorubicin
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HER 2 receptor monoclonal antibodies e.g. trastuzumab
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Antimetabolites e.g. 5 fluorouracil
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Immune checkpoint inhibitors e.g. ipilimumab
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Cardio-oncology

Cardio-oncology services arose in response to the identification of CTR-CVT and an increasing number of long-term cancer survivors affected by cardiovascular disease. The overarching aim is to allow patients with cancer to receive the best possible cancer treatment safely1. This involves a baseline cardiovascular risk assessment, surveillance and management of acute CTR-CVT during cancer treatment and guidance on management of long-term cardiovascular complications on completion of treatment.

The CTR-CVT graph (figure. 1) shows the timing of highest cardiovascular toxicity risk during cancer treatment. This often coincides with perioperative patients undergoing neoadjuvant therapy prior to cancer surgery. The cardio-oncology goals to minimise CTR-CVT and overall cardiovascular risk profile conveniently align with the period of perioperative optimisation of cardiac risk factors during prehabilitation.

Figure 1: Cardiovascular toxicity risk of patients over time, with the potential effect of cardioprotective strategies to reduce risk (arrows)2.

The majority of cardiotoxicity syndromes manifest within the first year of oncological treatment, which forms the majority of patients presenting for cancer surgery. The oncological factors that increase the risk of cardiotoxicity can be grouped into three categories3:

Patient factors
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Oncological factors
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Objective biomarkers
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Delayed cardiotoxicity occurring 12 months or more after completion of oncological care is less likely to be encountered in the prehabilitation setting. A history of previous cancer therapies should be enquired for in a patient presenting with features of heart failure in the perioperative period.

Screening and assessment

The initial assessment of cardiovascular toxicity risk involves:

  1. Evaluation of the patient’s baseline cardiac risk factors
  2. Understanding the cardiovascular implications of a specific tumour aetiology
  3. Identification and treatment of unwanted cardiac side effects of oncological treatment.

This framework aims to reduce long term cardiovascular risk in cancer patients.

Routine perioperative cardiovascular risk evaluation utilising history, examination and investigations forms the foundation of a baseline cardiovascular toxicity risk assessment2.

  • History of smoking, alcohol intake, diabetes, hypertension, dyslipidaemia, obesity, renal impairment and presence of existing cardiac disease
  • Enquiry should be made for symptoms of exertional dyspnoea, chest pain, palpitations, pre-syncope/syncope, orthopnoea, paroxysmal nocturnal dyspnoea and peripheral oedema
  • Evaluation of functional status through the Duke Activity Status Index (DASI) with a score ≤34 indicating increased risk of perioperative complications
  • Cardiovascular examination including pulse, BP, SpO2, presence of murmurs, JVP, peripheral oedema
  • Baseline cardiac investigations: ECG, FBC, U&E, HbA1c and BNP and troponin if appropriate (see section on biomarkers below).

Biomarkers

A combination risk assessment includes clinical history and assessment of functional capacity as above, and measurement of biomarkers:

  • B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP)

and/or

  • high-sensitivity cardiac troponins I or T (cTn I or cTn T).

Cardiac biomarkers can be measured in patients with cardiac risk factors, known/suspected cardiac disease or cardiotoxicity who are scheduled to undergo intermediate or major surgery2,4,5,6,7,8.

These tests may be used to risk stratify, guide the need for further cardiac testing pre-operatively, advise shared decision making and inform perioperative management such as the level of postoperative care/monitoring (eg HDU or ward) or pre-operative referral to perioperative medicine services for shared post-operative care.

High sensitivity cardiac troponins I and T (cTn I and cTn T)
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B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP)
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NT-proBNP Measurement and Perioperative risk of MACE or MINS (Adapted from Duceppe et al 2020) (8)
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Figure 2. 2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline6 – One potential approach to perioperative cardiovascular risk assessment

Referral and specialised cardiac investigations

The choice of cardiac investigation to answer a specific clinical question is influenced by availability, cost and level of accuracy required. Each investigation will have specific advantages and disadvantages (see table below).

A referral to a cardiologist is recommended prior to arranging any specific investigation.

MUGA
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Echocardiogram
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Advanced echocardiogram
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Cardiac CT
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Cardiac MRI
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Carcinoid heart disease

Carcinoid heart disease can occur in patients with carcinoid syndrome secretory neuroendocrine tumours. Cardiac involvement is present in 37% of patients with carcinoid syndrome and typically leads to tricuspid regurgitation, pulmonary stenosis and/or pulmonary hypertension. An echocardiogram is required to determine the presence of valvular disease, pulmonary hypertension and left and right ventricular function. 5-HIAA levels can be useful as carcinoid heart disease is almost never seen if 5-HIAA levels are below 50mg/24 hours9.

Hepatic resection of metastatic carcinoid cancer can prolong survival and control symptomatic endocrinopathy10. The increased central venous pressure associated with tricuspid regurgitation significantly increases surgical risk due to increased blood loss during liver resection. Valve replacement should be considered if transpulmonary gradient is ≥10mmHg. It is safe and is association with similar outcomes as patients without carcinoid heart disease undergoing hepatic resection for carcinoid syndrome11.

References
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Acknowledgements

Co-Principal Investigators:

  • A/Prof Alicia Martin – Director of Allied Health, Peter MacCallum Cancer Centre
  • Jenelle Loeliger – Manager Nutrition and Speech Pathology, Peter MacCallum Cancer Centre

Project Manager: ​

  • Dr Christina Prickett​ – Clinical Psychologist, Peter MacCallum Cancer Centre

Project team:​

  • Dr Rajib Ahmed​ – Consultant Anaesthetist, Peter MacCallum Cancer Centre
  • Professor Linda Denehy​ – Head of Allied Health Research, Peter MacCallum Cancer Centre
  • Ben de Zoete – Manager Physiotherapy & Occupational Therapy, Peter MacCallum Cancer Centre
  • Dr Lara Edbrooke – Allied Health Research Development Lead, Peter MacCallum Cancer Centre
  • Dr Maria Ftanou – Director of Psychosocial Oncology, Peter MacCallum Cancer Centre
  • A/Prof Hilmy Ismail – Anaesthetist, Peter MacCallum Cancer Centre
  • Professor Berhard Riedel​ – Director of Anaesthetics, Perioperative and Pain Medicine, Peter MacCallum Cancer Centre
  • Catherine Sinton​ – Clinical Nurse Consultant, Peter MacCallum Cancer Centre
  • Anya Trail​l – Manager Physiotherapy & Occupational Therapy, Peter MacCallum Cancer Centre

Communications Advisor:

  • Maddison Gray – Communications & Media Specialist, Western & Central Melbourne Integrated Cancer Services (WCMICS)

Clinical content leads: ​

  • Dr Raj Ahmed – Consultant Anaesthetist, Peter MacCallum Cancer Centre
  • Anna Beaumont – Dietitian, Peter MacCallum Cancer Centre
  • Jess Crowe – Physiotherapist, Peter MacCallum Cancer Centre
  • Dr Fiona Lynch – Clinical Psychologist, Peter MacCallum Cancer Centre
  • Lisa Nguyen – Physiotherapist, Peter MacCallum Cancer Centre
  • Catherine Sinton – Clinical Nurse Consultant, Peter MacCallum Cancer Centre

Steering committee members:

  • Dr Rajib Ahmed​ – Consultant Anaesthetist, Peter MacCallum Cancer Centre
  • Michael Barton – Deputy Manager, Western & Central Melbourne Integrated Cancer Services (WCMICS)
  • Hollie Bevans – Senior Dietitian, Western Health
  • Professor Linda Denehy​ – Head of Allied Health Research, Peter MacCallum Cancer Centre
  • Janelle Devereux and Bianca Bell – Executive Director, Health Systems Integration, North West Melbourne Primary Health Network (NWMPHN)
  • Ben de Zoete – Manager Physiotherapy & Occupational Therapy, Peter MacCallum Cancer Centre
  • Dr Lara Edbrooke – Allied Health Research Development Lead, Peter MacCallum Cancer Centre
  • Dr Maria Ftanou​ – Director of Psychosocial Oncology, Peter MacCallum Cancer Centre
  • Mr Michael Hii – Deputy Director, HPB and Upper GI Surgery, St Vincent’s Hospital Melbourne
  • A/Prof Hilmy Ismail​ – Anaesthetist, Peter MacCallum Cancer Centre
  • Drew Kenneady – Consumer Representative
  • Mainak Majumdar – Director, Critical Care, Mercy Health
  • A/Prof Alicia Martin ​- Director of Allied Health, Peter MacCallum Cancer Centre
  • Sharyn McGowan – Allied Health Team Leader, Bendigo Health
  • Fiona McKinnon – Director of Allied Health, St Vincent’s Hospital Melbourne
  • Orla McNally – Surgeon, The Royal Women’s Hospital
  • Jenelle Loeliger – Manager Nutrition and Speech Pathology, Peter MacCallum Cancer Centre
  • Denise Mitchell – Consumer Representative
  • Kathryn Pierce – Western Health Allied Health Representative, Western Health
  • Amanda Piper – Head of Cancer Strategy, Cancer Council Victoria (CCV)
  • Dr Christina Prickett​ – Clinical Psychologist, Peter MacCallum Cancer Centre
  • Professor Berhard Riedel​ – Director of Anaesthetics, Perioperative and Pain Medicine, Peter MacCallum Cancer Centre
  • Catherine Sinton​ – Clinical Nurse Consultant, Peter MacCallum Cancer Centre
  • Anya Trail​l – Manager Physiotherapy & Occupational Therapy, Peter MacCallum Cancer Centre
  • Chris White – Director, Cancer Centre, Bendigo Health

Contributions to content:

  • Shaza Abo – Physiotherapist, Peter MacCallum Cancer Centre
  • Dr Diva Baggio – Haematology Laboratory Registrar, Peter MacCallum Cancer Centre
  • A/Prof Cherie Chiang – Endocrinologist & Internal Medicine Consultant Physician, Peter MacCallum Cancer Centre
  • Professor Linda Denehy​ – Head of Allied Health Research, Peter MacCallum Cancer Centre
  • Dr. Amy Dennett – Physiotherapist, La Trobe University
  • A/Prof Helena Frawley – Principal Research Fellow, Allied Health, University of Melbourne
  • Dr Margaret He – Consultant Anaesthetist, Tauranga Hospital, New Zealand
  • Dr Nicolette Holt – Respiratory, Sleep & Perioperative Consultant Physician, Peter MacCallum Cancer Centre
  • A/Prof Hilmy Ismail​ – Consultant Anaesthetist, Peter MacCallum Cancer Centre
  • Ms Alana Jones – Enhanced Recovery after Surgery Nurse Coordinator, Royal Melbourne Hospital
  • Erin Laing – Dietitian, Peter MacCallum Cancer Centre
  • Dr Debra Leung – Consultant Anaesthetist, Peter MacCallum Cancer Centre
  • Tennille Lewin – Centre for Health Services Research, Peter MacCallum Cancer Centre
  • Celia Marsten – Occupational Therapist, Peter MacCallum Cancer Centre
  • Dr Walston Martis – Consultant Anaesthetist, Peter MacCallum Cancer Centre
  • Dr Mark Nolan – Consultant Cardiologist, Peter MacCallum Cancer Centre
  • Dr Chad Oughton – Consultant Anaesthetist, Peter MacCallum Cancer Centre
  • Ella Sexton – Clinical Psychologist, Peter MacCallum Cancer Centre
  • Dr Emma Tyson – Consultant Anaesthetist, Peter MacCallum Cancer Centre
  • A/Prof David Westerman – Consultant Haematologist, Peter MacCallum Cancer Centre
  • A/Prof Jamie Young – Pain & Rehabilitation Consultant Physician, Peter MacCallum Cancer Centre

The project team sincerely thanks all participants from various stages of this project:

  • The consumers, health professionals and other experts who participated in the co-design workshops
  • The health professionals and patients from the three implementation sites including Western Health, Bendigo Health and St Vincents Hospital Melbourne.


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