By Nancy Keene and Dr. Kevin Oeffinger MD
Important: This article appears in the Fall 2000 Candlelighters Childhood Cancer Foundation Newsletter (downloadable as a pdf file on the Candlelighters web site). It is reproduced here with the permission of Ruth Hoffman, Executive Director and Newsletter Editor of CCCF.
Anthracyclines, such as Adriamycin, are a group of chemotherapy medications used to treat a variety of childhood cancers. Use of anthracyclines has resulted in significantly increased rates of survival, but can also lead to a problem with the heart that may not show up until 1015 years after treatment. Because some survivors are at higher risk for developing heart problems than others and because tests are available that can pick up the problem at an early stage, it is important for each childhood cancer survivor to find out his/her individual risk.
The heart is a large muscle that is divided into four chambers and is designed to pump the blood around the body. The upper chambers or rooms are called atria and the lower chambers are called ventricles. The blood returning from the body enters the right atrium, is squeezed into the right ventricle, and then is pumped into the blood vessels in the lungs. It is here that the oxygen we breathe is transferred into many small blood vessels in the lungs. The blood, now rich with oxygen, returns to the left atrium and then is squeezed into the left ventricle, the largest and most powerful of the chambers. The left ventricle contracts to circulate the blood to the entire body.
The cells of the heart muscle are called cardiomyocytes (cardio = heart, myo = muscle, cytes = cells). In ways that are not well understood, anthracyclines can cause damage to the cardiomyocytes of the left ventricle. Over time, this can lead to thinning of the outside wall or muscle of the left ventricle, resulting in a stiff, noncompliant (loss of normal resiliency) left ventricle. The medical term for this condition is cardiomyopathy (cardio = heart, myo = muscle, pathy = abnormal, weakened).
Generally, this is not a problem while at rest, but when the heart needs to work harder, such as during exercise or strenuous physical activity, the stiff left ventricle may not be capable of increased pumping action. If this happens, the blood that is being pumped through the left side of the heart (atrium and ventricle) does not get pumped out fast enough and some of it "backlogs" in the small blood vessels of the lungs. Remember that the oxygen in the lungs is transferred to these small blood vessels, and so when the vessels become engorged with the backlogged blood, the oxygen can not be transferred properly. Though this problem, called congestive heart failure, can be quite serious, there are medications that can help.
Who is at risk?
Over half of the survivors who received anthracyclines (Adriamycin - doxorubicin; Cerubidine daunorubicin; Idamycin idarubicin) will have some damage to the heart muscle that can be detected with sophisticated testing. The percentage of survivors with some damage who will experience progressive weakening of their heart muscle and develop congestive heart failure is not known. It is likely that most survivors who have mild changes in heart functioning will not have increasing damage and will never develop symptoms. Long-term studies following survivors for many years are needed to help us better understand the process and factors that may worsen heart function. From studies to date, we know that patients treated with moderate to high dosages of an anthracycline are at higher risk. Use of chest/mantle radiation along with an anthracycline further increases the risk. In addition, females and survivors treated at a younger age (before 5 years old) are generally more likely to have problems than males or survivors treated at an older age.
What are the symptoms of a heart problem from an anthracycline?
Possible symptoms of congestive heart failure include:
These symptoms may be caused by a variety of other medical conditions, so it is very important to see a physician if you have any of these symptoms.
Is there anything that could worsen the weakened heart muscle or make me symptomatic?
Yes, the following things can potentially worsen a cardiomyopathy:
So now that you have scared me with all of this information, what should I do?
It is not our intent to scare survivors with these facts and figures, but rather to educate the reader about potential long-term risks related to previous treatment. Many survivors have no heart damage. Many of those who do show damage have no progressive weakening of the heart muscle. However, it is very important to find out about your individual risk. In a past column [see CCCF Newsletter], we discussed the value of each survivor obtaining a summary of his/her previous cancer treatment, including a list of chemotherapy medications. If you have a list, see if you received an anthracycline (Adriamycin - doxorubicin; Cerubidine daunorubicin; Idamycin idarubicin). If you didnt, this is not a problem you need to worry about. If you did (or if you are not sure), see your doctor and discuss your risk. Although recommendations vary, many institutions recommend periodic testing for survivors who had 175 mg/m2 or more of an anthracycline after the age of five. Those who received any anthracyclines before the age of five require life-long periodic testing.
If you are at risk, the most common test that is ordered to evaluate the heart for cardiomyopathy is an echocardiogram. This test is like an ultrasound of the heart and allows a cardiologist (heart specialist) to measure the thickness of the muscle of the left ventricle and to assess the pumping ability of the heart. The two primary measures used to assess the function of the left ventricle, the main pumping chamber of the heart, are the ejection fraction and the shortening fraction. The ejection fraction is a ratio, calculated by measuring the amount of blood that is pumped out with each beat and dividing it by the amount of blood that waits for the next cycle. Generally, a normal ejection fraction is considered to be above 60%. A decrease in the shortening fraction usually precedes a detectable decrease in the ejection fraction. The shortening fraction is also a ratio, determined by the diameter change of the left ventricle between the relaxation and the contraction phases divided by the diameter of the left ventricle in the relaxation phase. Above 30% is considered normal, with 26 to 30% representing a mild decrease in function.
If I have a problem with the heart muscle is there anything that can be done to help?
Yes. First, knowing that there is a problem allows your doctor to evaluate you more often and have a better idea of when and if the weakening of your heart muscle will become symptomatic and affect your life. This is especially important for female survivors who want to get pregnant. Second, there is a group of medications, called angiotensin converting enzyme (ACE) inhibitors, that have been very successful in helping patients with other types of cardiomyopathies. A current multi-institution study, funded by the National Institutes of Health, is evaluating one of the ACE inhibitors, enalapril, to see if it helps to improve the function of heart muscle that has been damaged by anthracyclines. Hopefully, this study and others to follow will provide some help for survivors with this late effect.
Nancy Keene is the author of Childhood Leukemia, Childhood Cancer (with co-author Honna Janes-Hodder), Your Child in the Hospital, Working with Your Doctor and Childhood Cancer Surivors (co-authored with Wendy Hobbie
RN and Kathy Ruccione). She is Chair of the Patient Advocacy Committee of COG (Children&Mac226;s Oncology Group) and mother of 12-year-old Kathyrn who is a survivor of high risk ALL and 10-year-old daughter Alison.
Dr. Kevin Oeffinger MD directs a multidisciplinary program for young adult survivors of childhood cancer at UT Southwestern at Dallas TX and is partially supported as a Robert Wood Johnson Foundation Generalist Physician Faculty Scholar. He enjoys backpacking, running and hiking with his wife Patty, 16 year old son Daniel and 13 year old daughter Ashley.
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