The following are key points to remember from this American Heart
Association Scientific Statement on the field of cardio-oncology. Of
note, this document does not provide evidence-based guidelines, but
rather presents a broad overview of cardio-oncology, discussing various
aspects of this nascent discipline including cardiotoxicity, structuring
a cardio-oncology service, training in cardio-oncology, and directions
in research:
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1. A wide range of chemotherapy agents including fluoropyrimidines,
taxanes, vinca alkaloids, platinum compounds, cyclophosphamide,
anthracyclines, bleomycin, and others are associated with vascular
complications extending from coronary vasospasms to thromboembolic
disease.
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2. Radiation therapy has acute vascular inflammatory effects, leading to
premature atherosclerotic disease and vasculopathies in irradiated areas
including venous stenosis and thrombosis. Other manifestations of
radiation-induced vascular damage includes dysautonomia, leading to
labile blood pressures and heart rate as well as orthostasis.
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3. Targeted therapies such as the small-molecule kinase inhibitors, while
dramatically altering cancer prognosis, can lead to endothelial injury
and dramatic rises in blood pressure, with related events such as
strokes, myocardial infarction, venous thromboembolism, and limb
ischemia. Immune checkpoint inhibitors (monoclonal antibodies to CTLA-4
and PD-1) have been associated with fulminant myocarditis.
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4. Cancer therapies also interfere with metabolism, leading to alterations
in glucose and lipid levels such as in the case of androgen deprivation
therapies, although their impact on outcomes is unclear.
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5. Venous thromboembolism, including superficial phlebitis, deep-venous
thrombosis, catheter-related thrombosis, and pulmonary embolism
represent the most common cardiovascular complication of malignancy, at a
rate sevenfold higher than noncancer patients. Patients with cancer
represent 20% of the overall venous thromboembolism burden. Low
molecular weight heparin for an extended duration that is undefined
remains the preferred therapy, although preliminary evidence suggests
direct oral anticoagulants are a safe alternative.
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6. Cancer and cardiovascular disease have shared risk factors that include
lifestyle, tobacco use, hyperlipidemia, inflammation, and certain
somatic mutations (DNMT3A, ASXL1, TET2).
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7. Cardio-Oncology research should be directed towards better understanding
of the off-target effect of kinase-inhibitors, and developing
personalized, risk-based approaches to primary prevention of
cardiovascular adverse events attributed to cancer therapy.
Collaboration between basic, translational, and clinical research
programs and the creation of multi-institutional registries is essential
to identify and characterize accurately cardiovascular toxicities of
cancer therapies.
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8. There is an unmet need for specialized cardiovascular services
addressing the needs of cancer patients across their treatment
continuum. Successful Cardio-Oncology services are rooted in a
collaborative multidisciplinary partnership between Cardiology and
Oncology in their various subspecialties.
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9. While several institutions have established training programs in
Cardio-Oncology, there is a need to define the core competencies to
standardize expertise across the field, similar to what has been done in
the past with other cardiovascular subspecialties.
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10. Clinical trial endpoints in oncology should be revised to allow for
accurate identification of cardiovascular and metabolic toxicities.
Given many cancer therapies are approved with only one trial,
post-marketing surveillance is essential to identify rare but serious
cardiovascular effects of these therapies.