Author + information
- Guilherme H. Oliveira, MD, MBA∗ ()
- Harrington Heart and Vascular Institute, University Hospitals and Case Western Reserve University School of Medicine, Cleveland, Ohio
- ↵∗Address for correspondence:
Dr. Guilherme H. Oliveira, Heart Failure and Transplant Center, Cardio-Oncology Center, University Hospitals Health System, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, Ohio 44106.
A multitude of observational studies have firmly established the association between chest irradiation and cardiovascular disease (1). The true nature of this association, however, has proven elusive for over 50 years. In the last third of the 20th century, radiation heart disease was confined to the few childhood lymphoma survivors lucky enough to reach early adulthood only to be diagnosed with valvular, coronary, or pericardial disease. Then, the risk of radiation was thought to be indolent; its consequences waited decades to materialize. More recently, however, female breast cancer survivors treated with chest radiation were found to display a dose-related incremental risk of major adverse cardiac events (MACE) within 5 years (2). Currently, the risk is thought to be subacute, with cardiac side-effects starting around 5 years. However, many details remain lacking. For example, what is the effect of baseline cardiovascular profile or established heart disease on radiation risk? What are the actual doses of radiation to the heart that impart risk and in whom? How early after radiation is this risk realized? Studies have thus far failed to provide data granular enough to allow a more complete appreciation of this association.
No more. In this issue of the Journal, Atkins et al. (3) present us with a Herculean effort at unraveling many of the most perplexing questions that have clouded our understanding of this disease (3). In their paper, the authors describe the relationship between mean heart dose of radiation and the incidence of MACE and all-cause mortality among 748 lung cancer patients in a single-center, prospectively followed cohort. There are several aspects of this study that elevate it above previous similar attempts, lending more potency to its findings.
First, the authors painstakingly combed all charts to determine the presence or absence of previous coronary heart disease (CHD) by interrogating notes, laboratory results, electrocardiograms, stress tests, coronary angiograms, and computed tomography scans. For those in whom heart disease could not be found, the authors manually calculated individual Framingham risk scores, thereby establishing a cardiovascular risk profile never before available in this population. Second, 2 of the coauthors manually reviewed individual radiation doses, recontoured the heart, and calculated mean heart dose for every patient. This effort was independently confirmed by a third investigator, providing by far the most accurate assessment of radiation dose to the heart of any cohort this size until now. Third, the authors used American College of Cardiology/American Heart Association definitions of MACE as the primary endpoint, as opposed to the less specific common terminology criteria for adverse events used in the majority of cancer trials. By using terms that are unequivocal to the cardiology community, the authors offer a higher degree of fidelity to the interpretation of cardiovascular outcomes.
Through their work, Atkins et al. (3) illuminate some of the unknowns of radiation heart disease and advance our understanding of the cardiovascular effects of radiation in lung cancer patients. They confirm that over one-third of patients with lung cancer have pre-existing CHD, alerting to the high coexistence of both diseases. They show that patients with pre-existing CHD have a higher risk of MACE than those without, in a dose-dependent fashion. They further demonstrate that median heart doses >10 Gy can increase both MACE and all-cause mortality in patients without heart disease, but for those with pre-existing CHD, any dose can augment the risk disproportionately. Most importantly, the authors teach us that adverse events occur very early—within 1 and 2 years of exposure—definitively laying to rest the notion that radiation to the heart has predominantly delayed effects.
In summary, Atkins et al. (3) provide us with the data on which to build an evidence-based cardiovascular approach to lung cancer patients—and perhaps any patient—receiving chest radiation. Based on their findings, these patients should be aggressively screened for CHD and, if present, mean heart dose should be minimized at all costs because no dose is totally safe. For patients without pre-existing heart disease, the Framingham Risk Score should be calculated and mitigated, and the mean heart dose should be kept to <10 Gy. The message is clear: in this day and age, no cancer patient undergoing chest radiation should fail to see a cardio-oncologist.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Oliveira has reported that he has no relationships relevant to the contents of this paper to disclose.
- 2019 American College of Cardiology Foundation