Hodgkin’s disease is a malignant disorder of lymphoid tissue that afflicts approximately 7,500 Americans each year.1 The disorder usually presents in people in early adulthood (ages 15 to 35 years) or in people aged 50 years and older who have lymphadenopathy in the neck or supraclavicular area and possibly low-grade fever, night sweats and weight loss. The results of a biopsy of the lymph nodes will indicate the presence of Reed-Sternberg cells, which may contain the Epstein-Barr virus. Depending on the stage of disease, treatment consists of the intravenous administration of chemotherapeutic agents and radiation therapy delivered to the neck, chest (mediastinum), abdomen and pelvis.
Dentists working in concert with physicians can provide dental treatment safely to patients with radiation-induced heart disease.
Breast cancer, a malignancy of the glandular tissue, is the most common cancer in North America and usually affects women between the ages of 40 and 70 years.2 Depending on the stage of disease, treatment consists of surgical procedures involving the breast, intravenous administration of chemotherapeutic agents and radiation therapy delivered to the breast, chest wall and axilla.
The heart is a radiosensitive organ and almost always is within the field of radiation and may undergo pathological changes depending on the radiation dose and the volume of cardiac tissue that is irradiated.3–6 These changes, which were not widely recognized until the 1990s, affect all components of the heart. Most germane to the practice of dentistry, however, is the damage sustained by the valvular apparatus and the coronary vessels. These complications often appear late, arising 10 to 20 years after therapy, and may not be recognized readily by the patient or even suspected by the primary care health provider.
 |
VALVULAR DISEASE
|
|---|
Mediastinal irradiation injures the endothelial cells in the capillaries of the heart’s microcirculation. This initially causes capillary swelling and fibrin formation, resulting in a compromise of blood supply (ischemia). This later is followed by fibrosis of tissues with resultant anatomical distortion and functional alterations.7–9 The process involving the heart valves is slow but progressive, and it often goes unrecognized for many years until, serendipitously, it is discovered that the patient has developed a heart murmur. The cusps or leaflets of the valves thicken, fibrose and on occasion partially calcify.10,11 Similarly, the chordae tendineae, which control valve leaflet movements, fibrose and shorten.12 The valves that are unable to close completely permit the leakage of blood in a retrograde fashion, producing regurgitation murmurs. On occasion, the valve orifice is narrowed simultaneously by fibrosis, thus impeding blood flow and producing a murmur of stenosis. The mitral and aortic valves on the left side of the heart are injured more commonly than are the tricuspid and pulmonic valves on the right side of the heart.13,14 This probably results from the irradiation technique and the fact that the left-sided mitral and aortic valves are subjected to greater trauma from the high pressure associated with the left ventricle and aorta, respectively. These structural changes increase the person’s risk of developing endocarditis.15–17
Mediastinal irradiation injures the endothelial cells in the capillaries of the heart’s microcirculation.
As radiation-associated valvular disease progresses, the dimensions of the left ventricle and atrium may increase, and the patient may become symptomatic and exhibit signs of heart failure. In the latter stages of the disease, valve replacement surgery may be necessary. People who have received prosthetic heart valve implants after their native valves sustained radiation damage are at even greater risk of developing endocarditis.18–20
Hodgkin’s disease.
Approximately 25 percent of the people who have received radiation therapy for Hodgkin’s disease develop heart murmurs five to 13 years after treatment.21 These murmurs, which are defined by echocardiography, usually are caused by aortic or mitral valve regurgitation or both. The concomitant administration of cardiotoxic chemotherapeutic agents does not appear to increase the risk of a patient’s experiencing valvular dysfunction. In fact, over the last decade the use of these medications has permitted a reduction in the dose and the size of the radiotherapy field. Because of the prolonged time that it takes to manifest valvular disease, however, it is not known if this refinement will result in a decreased prevalence of valvular disease.22
Breast cancer.
The frequency of valvular disease brought on by radiation therapy used to treat breast cancer is undocumented. However, in the largest and most recent study of heart valve operations performed after radiation therapy, there were more patients who had had breast cancer than those who had had Hodgkin’s disease.23 This is despite the fact that patients who received radiation therapy to treat breast cancer received lower doses of radiation to smaller volumes of heart tissue.24 As in Hodgkin’s disease, the aortic and mitral valves were the valves that most often showed signs of radiation damage.25–30
|
CORONARY ARTERY DISEASE
|
|---|
Standard therapeutic doses of radiation can cause endothelial proliferation, fibroblast proliferation, collagen deposition and fibrosis, all of which are within the large branches of the coronary arteries. These changes can lead to an accelerated form of atherosclerosis and an increased risk of experiencing nonfatal and fatal myocardial infarctions. The microvasculature supplying the myocardium likewise is fibrosed by the radiation therapy, compounding the issues of cardiac ischemia and death.31 Therapy consists of the administration of antianginal medication, angioplasty or coronary artery bypass grafting.32
Hodgkin’s disease.
Clinically significant coronary artery disease, or CAD, has been documented in children and adolescents treated with mediastinal irradiation for Hodgkin’s disease. They have an 8 percent risk of experiencing a fatal or nonfatal myocardial infarction at 22 years after therapy. Adults who receive radiation therapy for Hodgkin’s disease do not appear to fare any better. Approximately 7 to 8 percent of these adults appear to develop severe CAD 11 to 18 years after treatment.33 The anterior portal of mediastinal radiation therapy most often damages the left main coronary artery; the left anterior descending artery, or LAD; and the ostium of the right coronary artery, while the posterior portal of radiation most often damages the circumflex artery.34 The administration of chemotherapeutic agents does not appear to influence this outcome.35–37 The risk is highest and the onset of disease is earliest in people who also have other atherogenic risk factors such as being 50 years of age or older, family history of CAD, hypertension, smoking habits, obesity, hyperlipidemia or diabetes, all of which are known to be associated with the development of CAD.38
Clinically significant coronary artery disease has been documented in children and adolescents treated with mediastinal irradiation for Hodgkin’s disease.
Breast cancer.
Studies of women treated by mastectomy and radiation therapy for cancer of either breast between 1949 and 1975 demonstrated that these women were at higher risk of dying of heart disease than were women whose treatment was limited to just the surgical procedure.39 Studies of women who received radiation therapy in the 1980s and early 1990s have confirmed these findings and noted that women receiving radiation therapy for left-sided breast cancer are at significantly greater risk of experiencing death from a myocardial infarction than are women who received radiation therapy for right-sided breast cancer. This discrepancy in risk between sides arises because the LAD branch of the coronary artery, which supplies the most vital area of the heart, lies on the left anterior wall of the heart and absorbs very high doses of radiation from a left-sided treatment.40,41 Women with left-sided disease who are at greatest risk are those who received radiation therapy 10 to 15 years earlier and those who received more extensive radiation therapy (including an increased dose and volume of irradiated cardiac tissues) because of the need to incorporate the internal mammary lymph nodes within the irradiation field.42 This increased risk of experiencing death from a myocardial infarction, however, is not influenced by the type of surgery (mastectomy versus lumpectomy) or by the administration of chemotherapeutic agents (for example, anthracyclines such as doxorubicin and epirubicin or cyclophosphamide) but rather by the amount of radiation absorbed by the heart—specifically the coronary arteries—and the presence or absence of other atherogenic risk factors.43–52
The issue of late-treatment complications arising from mediastinal irradiation has taken on even greater significance in recent years. Today, large numbers of relatively young women with a long life expectancy are being diagnosed with early breast cancer by mammographic screening and are receiving radiation treatment.53–55 Radiation oncologists have hypothesized that these women may be at less risk of developing radiation-induced heart disease than were women treated in earlier decades because of the improvements in techniques such as tangentially directed energy beams focused on the residual breast rather than the chest wall and heart, modified fractionation (the time interval over which treatment is delivered) and better cardiac shielding, all of which spare substantial volumes of the heart from high doses of radiation. These advances may lessen the prevalence rate of radiation-induced heart disease, though it probably is too early to know with certainty because the follow-up interval to date has been relatively short.
|
DENTAL MANAGEMENT CONSIDERATIONS
|
|---|
People with a history of receiving mediastinal irradiation to treat malignant disease often develop an occult, progressive form of heart disease that is free of subjective symptoms in its early stages. Therefore, when obtaining medical histories, dentists should ask all patients, "Have you ever had radiation treatment for a tumor, cancer or other condition?" If invasive and possibly stressful dental procedures are planned, dentists should ask patients who respond positively to this question and who say that they have received mediastinal irradiation to have the structure and function of their hearts evaluated by a physician (preferably a cardiologist) who is familiar with radiation-induced cardiovascular disease.56 When dentists explain the need for the consultation to the patient, they should do it in a manner that does not unduly provoke anxiety. The physician should be informed of these needed invasive dental procedures and be asked to comment on the patient’s need for prophylactic antibiotics and sedative medications and to prescribe any perioperative cardiac medications.
The physician initially will confirm the patient’s medical history, perform a comprehensive physical examination and order the necessary laboratory tests. The physician next will auscultate the patient’s heart for any abnormal sounds such as murmurs or gallops and analyze an electrocardiogram for rhythm disturbances, signs of cardiac enlargement and ischemia. A chest radiograph and an echocardiogram also may be ordered. The chest radiograph can be evaluated for signs of cardiac enlargement and pleural effusion, and the echocardiogram can be used to evaluate the dimensions of the heart wall, chamber size, valve function and aberrant blood flow patterns about the valves.57
Patients who have been found by their physicians to have developed radiation-induced valvular disease of such an extent that they are at risk of developing endocarditis from certain dental procedures will need to be prescribed antibiotic prophylaxis and antiseptic mouthrinse. In general, prophylaxis is recommended for procedures associated with significant bleeding from hard or soft tissues such as extractions, periodontal surgery, scaling and professional teeth cleaning (Box
).58 Adult patients who are not allergic to penicillin should be administered 2 grams of amoxicillin orally one hour before the procedure. Adult patients who are allergic to penicillin should be administered 600 mg of clindamycin, 2 g cephalexin or 500 mg of azithromycin orally one hour before the procedure. They also should be administered 15 milliliters of chlorhexidine to rinse with for 30 seconds just before the dental treatment begins. Furthermore, because endocarditis may occur in spite of appropriate prophylaxis, patients should be told to report back to the dental office if they develop an unexplained fever, night chills, weakness, myalgia, arthralgia, lethargy or malaise after treatment.59–62
TOP
ABSTRACT
VALVULAR DISEASE
