Cardio-Oncology: Vascular and Metabolic Perspectives

Campia U, Moslehi JJ, Amiri-Kordestani L, et al., on behalf of the American Heart Association Council on Peripheral Vascular Disease; Council on Arteriosclerosis, Thrombosis and Vascular Biology; and Council on Cardiovascular and Stroke Nursing.
Cardio-Oncology: Vascular and Metabolic Perspectives: A Scientific Statement From the American Heart Association. Circulation 2019;Feb 21:[Epub ahead of print].

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:

  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.
  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.
  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.
  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.
  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.
  6. Cancer and cardiovascular disease have shared risk factors that include lifestyle, tobacco use, hyperlipidemia, inflammation, and certain somatic mutations (DNMT3A, ASXL1, TET2).
  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.
  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.
  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.
  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.

Keywords: Anthracyclines, Antibodies, Monoclonal, Anticoagulants, Antineoplastic Agents, Bleomycin, Blood Pressure, Cardiotoxicity, Constriction, Pathologic, Coronary Vasospasm, Cyclophosphamide, Glucose, Heparin, Low-Molecular-Weight, Hyperlipidemias, Inflammation, Lipids, Metabolic Syndrome, Myocardial Infarction, Myocarditis, Phlebitis, Primary Dysautonomias, Primary Prevention, Pulmonary Embolism, Stroke, Thrombosis, Tobacco Use, Vascular Diseases, Venous Thromboembolism, Venous Thrombosis

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