Guidance to Help Cancer Survivors Avoid Cardiac Death

Janis C. Kelly

September 26, 2014

Oncologists and cardiologists need to work more closely to protect cancer patients from the cardiovascular complications of cancer treatment, according to an expert consensus statement published in the September issue of the Journal of the American Society of Echocardiography.

"Once patients have survived cancer, they don't die from cancer, they die from heart disease. Cardio-oncology is about making sure that doesn't happen," said Juan Carlos Plana, MD, professor of medicine at Baylor College of Medicine in Houston, who was chair of the expert consensus panel.

The guidance recommends the proactive use of echocardiography and biomarker monitoring, among other strategies.

The recommendations cap several years of work by a joint task force of the American Society of Echocardiography and the European Association of Cardiovascular Imaging.

Concern about cancer therapeutics-related cardiac dysfunction (CTRCD) originated with the recognition of anthracycline-associated heart failure.

But concern has broadened because of the range of potentially heart-damaging drugs now used in cancer treatment, the growing number of cancer survivors for whom cardiac damage is an issue, and the recognition that cardiac damage might not become apparent until decades after cancer treatment.

The panel defines CTRCD as a decrease of more than 10% in left ventricular ejection fraction (LVEF) to a value below 53% of normal, confirmed with repeated cardiac imaging 2 to 3 weeks later.

CTRCD is classified according to the mechanism of toxicity. Type I CTRCD, such as that caused by doxorubicin, is dose-dependent, usually occurs soon after the administration of the cardiotoxic agent, and is irreversible because it causes cell apoptosis. Early detection and treatment are the key to preventing left ventricular remodeling and heart failure.

Type II CTRCD, such as that caused by trastuzumab (Herceptin, Roche/Genentech), is not dose-dependent and is often reversible because (in the absence of combination treatment with a type I agent) it does not lead to apoptosis.

Recommended: Imaging and Biomarkers

The consensus panel recommends an integrated approach that combines imaging and biomarker analysis, and suggests that a baseline echocardiograph be obtained for all patients prior to initiation of cancer therapy.

The panel acknowledges that such an approach might not be feasible, but strongly recommends baseline cardiac assessment for those with established cardiovascular disease or left ventricular dysfunction and for those who are older than 65 years or who are scheduled to receive more than 350 mg/m² of a type I agent or combination therapy with type I and type II drugs.

The baseline cardiac assessment should include electrocardiography to evaluate cardiac rhythm and to detect signs of resting ischemia, and a cardiac imaging test (usually echocardiography) for the evaluation of cardiac structure and function.

The panel also recommends baseline assessment of global longitudinal strain (GLS), a measure of left ventricular deformation, and/or of troponin levels, a biomarker for myocardial injury.

According to the recommendations, cardiology consultation should be considered if LVEF is below 53%, GLS is below the limit of normal, or troponin levels are elevated.

This proactive imaging protocol is extremely helpful.

"This proactive imaging protocol is extremely helpful as it provides an accurate starting point for the patient's normal cardiovascular health and offers the clinician early detection and warning should there be any adverse changes during the cancer treatment," said Dr. Plana.

For patients treated with anthracyclines or other type I agents, the panel recommends follow-up testing at the completion of therapy for doses below 240 mg/m² and before each additional treatment cycle after exceeding 240 mg/m². This is a marked a change from an earlier assumption of a 400 mg/m² threshold for anthracycline-associated heart failure risk, the panel points out.

Patients treated with trastuzumab or other type II agents should undergo follow-up echocardiography every 3 months during therapy.

If trastuzumab follows an anthracycline regimen, the recommended baseline evaluation should include LVEF, GLS, and troponin, which should be repeated every 3 months during treatment and 6 months after treatment.

In light of the potential hemodynamic burden of the tyrosine kinase inhibitors sunitinib (Sutent, Pfizer) and sorafenib (Nexavar, Bayer) in patients with known coronary artery disease, the panel urges that clinicians monitor blood pressure and symptoms closely. "In the absence of data, we recommend a baseline echocardiographic evaluation, with follow-up at 1 month and every 3 months while on therapy with VEGF or VEGF-receptor inhibitors," they write.

The panel recommends that during chemotherapy, patients be monitored for subclinical left ventricular dysfunction, which is a harbinger of more severe heart damage. Cardiology consultation should be considered if abnormal GLS or elevated troponin levels (compared with baseline) develop.

Cardiac MRI, although not universally available, is recommended if chemotherapy discontinuation is being considered because of CTRCD.

Additional imaging for CTRCD is not needed in patients with no additional risks (such as radiotherapy), stable GLS during chemotherapy, normal GLS 6 months after completion of treatment with a type I chemotherapy, or negative troponin levels during therapy.

The panel concludes that "after the completion of therapy, and particularly in patients who were not followed using a strategy of early detection of subclinical left ventricular dysfunction, this committee suggests a yearly clinical cardiovascular assessment by a healthcare provider, looking for early signs and symptoms of cardiovascular disease, with further cardiac imaging ordered at the discretion of the provider."

Dr. Plana has disclosed no relevant financial relationships. Some of the panel members report financial relationships with pharmaceutical and/or imaging companies.

J Am Soc Echocardiogr. 2014;27:911-939. Full text


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