In 2022, the European Society of Cardiology (ESC) published a guideline on cardio–oncology, developed in collaboration with the European Hematology Association, the European Society for Therapeutic Radiology and Oncology, and the International Cardio–Oncology Society.
This specialist Guidelines overview for secondary care cardiologists and oncologists provides a summary of the key recommendations from the guideline on the cardiovascular (CV) health of patients before, during, and after cancer therapy. It includes assessment, risk-stratification, prevention, and management of cancer therapy-related CV toxicity (CTR–CVT), and the management of CV disease (CVD) caused directly or indirectly by cancer. In an accompanying commentary, Professor Simon Ray assesses the significance of the guidance for cardiology and oncology.
Please refer to the full guideline for all of the recommendations, rationale, and background information.
Key Takeaways From the Guideline
- Integration is a guiding principle of cardio–oncology; cardio–oncology providers must have knowledge of the broad scope of cardiology, oncology, and haematology, and communication between different healthcare professionals is critical to optimise patient care
- Cardio–oncology programmes minimise unnecessary interruptions to cancer treatment as well as cancer therapy-related cardiovascular toxicity
- Multidisciplinary team discussion should balance the risks and benefits of stopping cancer treatment for patients who develop cardiovascular toxicity
- Baseline cardiovascular risk assessment is recommended for all patients with cancer who are due to receive a potentially cardiotoxic anticancer therapy
- Measures are needed for both primary and secondary prevention of cardiovascular toxicity
- A cardio–oncology team must coordinate long-term follow up of cardiovascular toxicity risk and surveillance planning once cancer therapy has finished
- Patients and their carers should be provided with guidance to promote healthy lifestyle and to recognise and report signs and symptoms of cardiovascular disease.
Risk Categorisation Prior to Cancer Treatment
- All patients should undergo CV toxicity risk stratification before starting potentially cardiotoxic anticancer treatment
- Consider using the Heart Failure Association and International Cardio–Oncology Society risk assessment
- Communicate results to patients and relevant healthcare professionals
- Patients with low CV toxicity risk should have anticancer therapy without delay
- Patients with moderate CV toxicity risk should be considered for referral to cardiology
- Patients with high or very high CV toxicity risk are recommended for cardiology referral, and the balance of risks and benefits of cardiotoxic anticancer therapy should be discussed by the multidisciplinary team before starting cancer treatment
- Patients with pre-existing CVD, or whose baseline CV toxicity risk assessment is abnormal, are recommended for cardiology referral.
Assessment and Monitoring
- All patients starting cancer therapy should have an electrocardiogram (ECG) as part of their baseline CV risk assessment, and those with abnormal results should be referred to a cardiologist
- Baseline measurements of natriuretic peptides and/or cardiac troponin should be taken before treatment if they will be measured during treatment to detect cancer therapy-related cardiac dysfunction. See the full guideline for specific recommendations in patients at differing levels of CV risk.
Cardiac Imaging Modalities in Patients with Cancer
- Echocardiography is the first-line recommendation for cardiac function assessment
- 3D echocardiography is recommended for left ventricular ejection fraction (LVEF) measurement
- Global longitudinal strain is recommended, if available
- Consider cardiac magnetic resonance (CMR) if echocardiography is unavailable or non-diagnostic
- Consider multigated acquisition nuclear imaging if transthoracic echocardiography is not diagnostic and CMR is unavailable
- Comprehensive baseline transthoracic echocardiography is recommended for all patients with high or very high CV toxicity risk.
Primary Prevention of Cancer Therapy-Related Cardiovascular Toxicity
- Manage CV risk factors before, during, and after cancer therapy as recommended in the 2021 ESC guideline on CVD prevention in clinical practice
- Consider statins for primary prevention in adults at high and very high CV toxicity risk
- When anthracycline chemotherapy is indicated for adults at high and very high CV toxicity risk, consider:
- liposomal anthracyclines
- Consider angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) and beta-blockers recommended for heart failure in high- and very high-risk patients receiving:
- anti-human epidermal receptor 2 (HER2) therapies
- targeted cancer therapies that may cause heart failure.
Secondary Prevention of Cancer Therapy-Related Cardiovascular Toxicity
- Management of CVD according to applicable ESC Guidelines is recommended before, during, and after cancer therapy.
Venous Thromboembolism Prophylaxis During Anticancer Treatment
- For patients undergoing major open or laparoscopic abdominal or pelvic surgery with high venous thromboembolism (VTE) risk and low bleeding risk, extended prophylaxis with low-molecular-weight heparin (LMWH) is recommended for 4 weeks post-operatively
- Prophylactic LMWH is recommended for the primary prevention of VTE in the absence of bleeding or other contraindications for:
- hospitalised patients
- patients undergoing prolonged bedrest
- patients with reduced mobility
- Consider prophylaxis with LMWH or a non-vitamin K antagonist oral anticoagulant (NOAC; apixaban or rivaroxaban) for ambulatory patients receiving systemic therapy at high risk of thrombosis, if there are no significant contraindications
- A specialist CV assessment is recommended for optimal diagnostic workup and management of patients who present with new CV toxicity during or after cancer treatment.
Management of Acute Coronary Syndromes in Patients Receiving Anticancer Treatment
- When cancer therapy is suspected as a contributing cause, a temporary pause in cancer therapy is recommended
- For patients with ST-segment elevation myocardial infarction (STEMI) or high-risk non-ST-segment elevation acute coronary syndromes (NSTE–ACS) with life expectancy of 6 months or more, an invasive strategy is recommended
- Consider a conservative non-invasive strategy for patients with STEMI or NSTE–ACS and poor cancer prognosis (life expectancy of <6 months) and/or very high bleeding risk
- Consider a short dual antiplatelet therapy strategy for patients with very high bleeding risk treated with percutaneous coronary intervention (PCI) for ACS
- Consider prasugrel or ticagrelor in patients treated with PCI for ACS that have excessive thrombotic risk and low bleeding risk
- In patients with cancer, thrombocytopaenia, and ACS:
- aspirin is not recommended if platelets are <10,000/mcl
- clopidogrel is not recommended if platelets are <30,000/mcl
- prasugrel or ticagrelor are not recommended if platelets are <50,000/mcl.
Management of Chronic Coronary Syndromes in Patients Receiving Anticancer Treatment
- Individualised duration of dual antiplatelet therapy is recommended for patients with chronic coronary syndromes following revascularisation, based on thrombotic/ischaemic and bleeding risk, type and stage of cancer, and current cancer treatment.
Management of Valvular Heart Disease in Patients Receiving Anticancer Treatment
- Manage patients with pre-existing severe valvular heart disease (VHD) or those who develop new VHD during cancer therapy according to the 2021 ESC/EACTS Guidelines for the management of valvular heart disease, taking cancer prognosis and patient preferences into consideration.
Management of Atrial Fibrillation in Patients Receiving Anticancer Treatment
- For risk stratification for systemic thromboembolism and stroke, consider the patient’s CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 [two points], diabetes mellitus, stroke [two points]—vascular disease, age 65–74 years, sex category [female]), bearing in mind that this may underestimate the actual thromboembolic risk
- In cancer patients with atrial fibrillation (AF):
- if the CHA2DS2-VASc score is ≥2/3 in men/women, respectively, long-term anticoagulation is recommended for the prevention of stroke or systemic thromboembolism
- if the CHA2DS2-VASc score is ≥1/2 in men/women, respectively, long-term anticoagulation should be considered for the prevention of stroke or systemic thromboembolism
- if the CHA2DS2-VASc score is ≥0/1 in men/women, respectively, therapeutic anticoagulation may be considered after consideration of the bleeding risk, as these patients may have a higher thrombotic risk than patients without cancer
- Reassessment of thromboembolic and bleeding risk is recommended during follow-up of cancer patients with AF
- In patients without a high bleeding risk, significant drug–drug interactions, or severe renal dysfunction, NOAC should be considered for stroke prevention in preference to LMWH or vitamin K antagonists (excluding patients with mechanical heart valves or moderate-to-severe mitral stenosis)
- For patients with AF and active cancer who are not suitable for NOAC, consider LMWH
- For patients with AF and contraindications for long-term anticoagulation, with a life expectancy of >12 months, left atrial appendage occlusion may be considered for stroke prevention
- Antiplatelet therapy or prophylactic LMWH are not recommended for the prevention of stroke or systemic thromboembolism in patients with AF and cancer
- For patients who develop well-tolerated AF while receiving active cancer treatment, consider heart rate control strategy (preferably with beta-blockers).
Management of Arterial Hypertension in Patients Receiving Anticancer Treatment
- Effective treatment of cancer therapy-induced arterial hypertension is recommended to avoid CV complications and interruption of cancer treatment
- A blood pressure (BP) target of 140/90 mmHg is recommended during cancer therapy but, if treatment is well tolerated, a 130/80 mmHg target may be considered
- A systolic treatment threshold of 140–160/90–100 mmHg can be considered in some asymptomatic patients with metastatic cancer, as long as BP is regularly monitored
- If systolic pressure is ≥180 mmHg or diastolic pressure is ≥110 mmHg, the competing cancer and CV risks should be evaluated. Cancer therapy associated with hypertension should be deferred or temporarily withheld until BP is controlled to 160/100 mmHg
- ACE-I or ARB are the first-line drugs for BP management in patients with cancer
- Dihydropyridine calcium channel blockers (CCB) are second-line
- For patients with BP of ≥160/100 mmHg, combination therapy with ACE-I or ARB and dihydropyridine CCB is recommended
- Diltiazem and verapamil are not recommended because of their drug–drug interactions. However, they may be considered for some patients who are intolerant to multiple antihypertensives, provided drug interactions are closely monitored.
Management of Venous Thromboembolism in Patients Receiving Anticancer Treatment
- Apixaban, edoxaban, or rivaroxaban are recommended for symptomatic or incidental VTE, provided there are no contraindications
- For patients with platelet counts >50,000/mcl, LMWH is recommended for symptomatic or incidental VTE
- For patients with platelet counts between 25,000 and 50,000/mcl, treatment with half-dose LMWH can be considered following discussion with the multidisciplinary team
- For selected patients with active cancer, extended anticoagulation beyond 6 months should be considered. This includes patients:
- receiving cancer treatment
- diagnosed in the past 6 months
- with progressive, advanced, or metastatic disease
- For patients with catheter-associated VTE, anticoagulation therapy is recommended for a minimum of 3 months, and for longer if the catheter remains in situ.
Management of Peripheral Artery Disease During Anticancer Treatment
- For patients who develop new symptomatic peripheral artery disease, a multidisciplinary approach is recommended to decide whether to continue or interrupt possible causative cancer therapy.
End-of-Cancer Therapy Cardiovascular Risk Assessment
- Educate and support patients to make healthy lifestyle choices and to recognise early signs and symptoms of CVD. Lifestyle advice should cover BP, cholesterol, quitting smoking, weight loss when appropriate, and exercise
- Assess CV risk in the first year following cancer therapy, and after, following the 2021 ESC guideline on CVD prevention in clinical practice
- For high-risk asymptomatic patients, cardiac biomarkers and echocardiography at 3 and 12 months after completing cancer therapy is recommended
- For moderate-risk asymptomatic patients, cardiac biomarkers and echocardiography within 12 months of completing cancer therapy should be considered
- For low-risk asymptomatic patients, cardiac biomarkers and echocardiography within 12 months of completing cancer therapy may be considered
- Refer patients to cardiology if an end-of-therapy assessment finds new cardiac symptoms or new abnormalities in echocardiography or cardiac biomarkers. Cardio–oncology referral is preferable, if available. Alternatively, refer to a cardiologist with expertise in managing CVD in patients with cancer
- Consider exercise stress echocardiography and/or cardiopulmonary exercise testing for selected patients with exercise intolerance persisting 12 months after cancer treatment who have a normal resting echocardiogram and cardiac biomarkers
- Consider targeted cardiac rehabilitation for cancer survivors with high CV risk
- For patients who develop severe cancer therapy-related cardiac dysfunction, long-term continuation of cardiac medication is recommended
- Treatment optimisation and CV follow up is recommended for patients who developed the following during cancer therapy:
- tyrosine kinase inhibitor-mediated hypertension
- vascular toxicities.
Cardiovascular Surveillance in Cancer Survivors
- Some patients require long-term surveillance for cardiovascular problems. These include:
- survivors of paediatric and young adult cancers treated with high doses of anthracycline chemotherapy and/or high doses of radiotherapy to the chest
- adult cancer patients who developed moderate or severe complications during treatment
- survivors of leukaemia, myeloma, or lymphoma who required a bone marrow transplantation
- patients on long-term cancer treatments with the potential to cause heart problems after years of treatment
- ECG follow-up is recommended for patients who developed QT lengthening or long QT syndrome during cancer therapy.
For details of the recommendations on CV surveillance and treatment in cancer survivors, please see the full guideline.
Expert Commentary on the Guidance
|The Importance of Cardio–Oncology Guidance: Getting the Balance Right|
Professor Simon Ray
The worlds of cardiology and oncology are colliding. Oncologists and haematologists have at their disposal a rapidly expanding array of drugs and radiation techniques that are transforming the treatment of many malignancies, and allowing long-term survival in conditions that previously carried a dismal prognosis. Many of these treatments impact the cardiovascular system, particularly in individuals with pre-existing cardiovascular disease, and may convey an increased lifelong risk of cardiovascular complications in apparently fully recovered survivors.
From a cardiology perspective, cardio–oncology is a rapidly emerging subspecialty, but all cardiologists need to be aware of the potential effects of cancer treatments on their area of practice, and on the management of cardiovascular conditions. Almost all sections of cardiology practice are impacted, and many cardiologists will already be relatively familiar with some of the more well-known effects. Patients undergoing treatment with fluoropyrimidines, such as fluorouracil and capecitabine, may present with acute coronary syndromes; those treated with anthracyclines may develop left ventricular dysfunction; and vascular endothelial growth factor antagonists are a well-recognised cause of hypertension. Less well recognised among many cardiologists is that numerous agents may prolong the QT interval and predispose to ventricular arrhythmias, and that myocarditis is associated with the use of immune checkpoint inhibitors. In addition, the direct effects of malignancy or its treatment may impact on the feasibility of cardiology treatments, for example, in patients with thrombocytopenia and acute coronary syndrome or severe symptomatic aortic stenosis.
The 2022 European Society of Cardiology Guideline on cardio–oncology is an impressive synthesis of current knowledge, and will increase awareness of the scope of the problems that may be encountered. It was developed in collaboration with the European Haematology Association, the European Society for Therapeutic Radiology and Oncology, and the International Cardio–Oncology Society. This collaboration is worth emphasising–one of the key principles of cardio–oncology is the need to integrate disparate disciplines to strike a balance between effective treatment of cancer and any increased cardiovascular risk. A cardiologist's role can be summed up as facilitating the most effective cancer treatment feasible. Initially, this involves risk stratification prior to any cancer treatment, and primary or secondary prevention strategies to minimise cardiovascular risk. During therapy, surveillance for potential toxicity is required, along with prompt treatment should this occur. Following successful treatment, there may be a need for lifelong surveillance or treatment to minimise long-term adverse effects. None of this is achievable without close communication between the different specialties involved, and a clear focus on the best interests of each individual patient.
The guidelines are detailed and comprehensive, and will be the key reference point for clinicians involved in the management of cancer patients at risk of cardiovascular events. This is a fast-developing field, and the authors are candid about the significant gaps in the evidence base, and the need for further research to underpin future iterations of the guidance.