First ESC Guidelines on managing cardiac toxicity related to cancer treatments

The inaugural European Society of Cardiology (ESC) Guideline on cardio-oncology, revealed at the ESC Congress 2022 in Barcelona, Spain, provides some much-needed information on the concurrent management of cancer and cardiovascular (CV) disease.

“Management of cancer therapy-related CV toxicity (CTR-CVT) has a tremendous impact on the type of anticancer therapies that patients can receive as well as the long-term morbidity and mortality outcomes of patients with cancer,” said the Guideline authors. [Eur Heart J 2022;doi:10.1093/eurheartj/ehac244]

The Guideline is an extensive 133-page document created through a collaboration between ESC and the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO), and the International Cardio-Oncology Society (IC-OS).

“The overarching goal of the cardio-oncology discipline is to allow patients with cancer to receive the best possible cancer treatments safely, minimizing [unnecessary cancer therapy interruptions and] CTR-CVT across the entire continuum of cancer care,” the authors added.

 

Baseline CV assessment prior to cancer therapy initiation

“The optimal time to consider CV disease prevention strategies in patients with cancer is at the time of cancer diagnosis, prior to the initiation of cancer treatment,” said Guideline task force co-chairperson Dr Teresa Lopez-Fernandez from the La Paz University Hospital, Madrid, Spain.

“[A] pre-assessment by the cardiologist must be performed urgently to minimize delays to starting cancer treatment,” she continued.

This baseline assessment of CV risk should be carried out for all patients who are scheduled to receive potentially cardiotoxic anticancer treatments. This would enable consideration of CV risk when deciding on cancer treatment and personalization of surveillance and follow-up. In addition, this would allow for patients to be educated on their CV risk.

Multidisciplinary management is vital in patients who have pre-existing complex CV disease which could potentially affect their cancer treatment.

“CV toxicity risk stratification must be performed without delaying cancer treatments and cardio-oncology referral is recommended in high-risk and very high-risk patients before anticancer therapy, unless there is an oncology emergency requiring immediate cancer treatment,” said Lopez-Fernandez.

 

Who should be monitored?

“CTR-CVT risk may vary according to cancer type and stage, anticancer drugs, doses, and underlying comorbidities,” said the authors. As such, the frequency of cardiac monitoring during cancer treatment should be individualized based on multiple factors including baseline risk, duration and dose of cancer therapy, and pre-existing CV disease.

Global longitudinal strain, 3D echocardiography, and cardiac biomarkers could help identify CV toxicity based on specific cancer treatments and baseline risk of CV toxicity, said the authors.

During the first year of cancer treatment, patients who developed a CV complication during treatment should be monitored to assess if the complication persisted following clearance of the cancer treatment.

Patients, survivors, and their caregivers also need to be counselled on the monitoring of CV health during cancer treatment. This includes minimizing risk factors (eg, quitting smoking, reducing alcohol intake, acquiring adequate exercise, consuming a balanced diet) as well as identification, and subsequent reporting, of symptoms of cardiac issues (eg, breathlessness, chest pain, palpitations, fainting).

 

When to pause/stop cancer treatment?

“Multiple factors influence the decision to continue or stop therapy including the magnitude and severity of the heart problem, how early or late in the cancer management plan the problem has developed and how many more treatment doses are proposed, the response of the cancer to the treatment, the options for cardioprotection and their predicted benefit, the range of alternative non-cardiotoxic cancer treatments available, and the patient’s preference and concerns,” noted Guideline co-chairperson, Dr Alexander Lyon from the Royal Brompton Hospital, London, UK.

Multidisciplinary team discussion is warranted to assess the benefit vs risk of cancer treatment discontinuation in patients who develop CTR-CVT, the authors noted.

 

Is long-term monitoring warranted?

“Long-term monitoring aims to detect and manage cardiac problems early to prevent severe complications in cancer survivors and avoid CV side effects in patients on long-term treatments,” said Lopez-Fernandez.

In the first year following cancer treatment, patients who received cardiotoxic anticancer therapies should be re-evaluated for CV toxicity. This assessment would also help guide long-term monitoring strategies.

 

Conclusion

“The risk of developing CTR-CVT depends on baseline [and non-baseline] CV condition and the type of treatment,” said Lopez-Fernandez, who highlighted that the risk of CV toxicity varies throughout the cancer care pathway.

The CV care strategy should be personalized based on each patient’s CV toxicity risk, cancer type and disease stage, and planned treatment.

The complete Guideline, available at https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac244/6673995, lists protocols for monitoring specific anticancer treatments including anthracyclines, HER-2 targeted and hormone therapies, immune checkpoint inhibitors, and chimeric antigen receptor T-cell therapy, as well as the management of CVR-CVT due to specific cardiac issues (eg, hypertension, coronary artery disease). It also provides recommendations for follow-up in patients who require long-term monitoring such as childhood cancer survivors and recipients of certain therapies, and management of CV issues in special populations (eg, patients with cardiac tumours, pregnant patients).

 

Class I level A recommendations in cancer patients   Many of the recommendations in the Guideline are based on level B or C evidence. However, the following recommendations were based on level A evidence. · Measure cardiac troponin levels at baseline in low- and moderate-risk patients following receipt of anthracycline chemotherapy but before initiation of anti-HER2-targeted therapies. · Use prophylactic low-molecular-weight heparin (LMWH) for at least the first 6 months of treatment in patients with multiple myeloma who have risk factors for venous thromboembolism (VTE). · Use apixaban, edoxaban, or rivaroxaban to treat symptomatic or incidental VTE in patients without contraindications. · Use LMWH to treat symptomatic or incidental VTE in patients with platelet count >50,000/μL. · Consider prolongation of anticoagulation therapy for >6 months in certain patients with active cancers including metastatic disease. · Monitor corrected QT interval at baseline and at 14 and 28 days in all patients receiving ribociclib. · Carry out cardiac magnetic resonance in patients with suspected amyloid light-chain cardiac amyloidosis.

 

Class III level C “what not to do” recommendations   · Avoid the use of QT-prolonging drugs during the acute phase of Takotsubo syndrome. · In patients with cancer, thrombocytopaenia, and acute coronary syndrome (ACS): Avoid aspirin if platelet count is <10,000/μL, avoid clopidogrel if platelet count is <30,000/μL, and avoid prasugrel or ticagrelor if platelet count is <50,000/μL. · In patients with atrial fibrillation, avoid antiplatelet therapy or prophylactic LMWH for stroke or systemic thromboembolism prevention. · Avoid diltiazem and verapamil for the treatment of arterial hypertension in patients with cancer due to drug–drug interactions.