Most children’s cancer survivors do not develop heart problems; however, certain types of cancer treatment can result in problems with the heart. Since heart problems may occur many years after cancer treatment, it is important for children’s cancer survivors to be aware of any treatments they received that can affect the heart. That way, they can take steps to keep their heart healthy, including regular medical check-ups and tests to monitor heart function. And if a problem develops, it can be detected and treated early.

The heart is a muscular organ that is the center of the body’s circulatory system. The heart is responsible for pumping blood with oxygen and nutrients to body tissues. There are four chambers (two atria and two ventricles) within the heart that work together to pump blood. Valves direct the flow of blood through the heart chambers and into the blood vessels. The rhythm of heart contraction and rate of the heartbeat are coordinated by nerves that send electrical impulses to different parts of the heart. A thin membrane (pericardium) surrounds and protects the heart and anchors it within the chest.

Heart Problems Following Treatment

• The muscle cells of the heart may be damaged so that the heart doesn’t pump normally (cardiomyopathy).
• The electrical pathways that conduct impulses to control heart rhythm may be scarred or damaged resulting in an abnormally fast, slow, or irregular heart beat (arrhythmias).
• The valves and blood vessels of the heart may be damaged, causing them to be stiff or to leak (valvular stenosis or insufficiency).
• The protective covering of the heart may become inflamed (pericarditis) or scarred (pericardial fibrosis).
• The blood vessels of the heart may become scarred or blocked (coronary artery disease), preventing delivery of oxygen and nutrients to the heart and other tissues.
• In severe cases, these problems may result in the death of heart tissue (heart attack or myocardial infarction) or an inability of the heart to pump blood properly (congestive heart failure).

Cancer Treatments that Cause Heart Problems

The heart can be affected by certain types of chemotherapy and by radiation therapy.

Anthracycline chemotherapy
The anthracyclines are a group of chemotherapy used to treat many children’s cancers. Commonly used anthracyclines include:

• Doxorubicin (Adriamycin.)
• Daunorubicin (daunomycin, Cerubidine.)
• Idarubicin (Idamycin.)
• Mitoxantrone (Novantrone.)
• Epirubicin

These chemotherapies can sometimes cause problems with heart muscle function (cardiomyopathy) and abnormal heart rhythms (arrhythmias). Patients who fall into the following categories may be at increased risk for heart problems.

• • Total anthracycline dose of 300 mg/m2 (milligrams per square meter of body surface area) or more when younger than 18 years of age
  • Total anthracycline dose of 550 mg/m2 or more when 18 years or older
  • Female
  • Of African descent
  • Treated before the age of 5, and especially those treated as infants
  • High doses of cyclophosphamide (Cytoxan) before a bone marrow or stem cell transplant
  • Treatment with Amsacrine, another chemotherapy drug that may affect the heart

Radiation therapy
Heart problems may result from radiation therapy to the heart or surrounding tissue. This includes radiation to the:

• Chest or thorax (including “mantle” and “mediastinal” treatment fields)
• Lungs
• Spine (chest or “thoracic” portion)
• Whole or upper abdomen
• Left kidney region (left flank or left upper abdomen)
• Total body (TBI)

Radiation therapy may result in scarring and stiffening of heart tissues, causing abnormal heart rhythm (arrhythmia) and problems with the heart muscle (cardiomyopathy), heart valves (valvular stenosis or insufficiency), blood vessels (coronary artery disease), and membrane surrounding the heart (pericarditis or pericardial fibrosis).

Patients who receive the following radiation at doses of 20 Gy (2000 cGy/rads) or more to the following areas (fields) may be at increased risk:

• Chest/thorax
• Mantle (from the chin to the upper abdomen)
• Mediastinal (central part of the chest)
• Lung
• Whole or upper abdomen
• Left kidney region (left upper abdomen or left flank)
• Receiving radiation to the spine at doses of 30 Gy (3000 cGy/rads) or higher
• Receiving total body irradiation (TBI)
• Receiving high doses of cyclophosphamide (Cytoxan) before a bone marrow or stem cell transplant
• Receiving anthracycline chemotherapy
• Receiving treatment with Amsacrine, another chemotherapy drug that may affect the heart
• Receiving treatment many years ago. (Modern radiation techniques using lower total doses and better heart shielding are less likely to cause damage.)

Other Risk Factors for Heart Problems

Some other medical conditions may also increase the risk of heart problems from chemotherapy or radiation therapy. These include obesity, high blood pressure, high cholesterol or triglyceride levels in the blood, and diabetes. Individuals may have a higher risk of having heart problems if these conditions run in their family. Heart disease is also more common in women who have gone through menopause, so female survivors who go through an early menopause may be at higher risk. Many health behaviors can add to the risk of heart disease including smoking, having an inactive (sedentary) lifestyle, and eating a diet high in fat.

Who is at Risk for Developing Heart Problems?

The risk of developing a heart problem after children’s cancer treatment is related to several factors:

• The age of the patient at the time of cancer therapy
• The total dose of anthracycline chemotherapy
• The total dose of chest radiation
• The amount of the heart tissue included in the radiation treatment field
• Treatment with other medications that affect heart function
• The presence of other conditions that affect heart function

Most children’s cancer survivors who were treated with anthracyclines or chest radiation have no heart damage at all. Some survivors have very mild changes in heart size or function that have not gotten worse over time. Only a small number of survivors have developed severe heart problems leading to heart failure or dangerous heart rhythms. Overall, the risk of developing heart problems after children’s cancer therapy is highest in survivors treated with higher doses of anthracyclines or chest radiation, especially those who received both treatments at a young age.

Doctors do not understand why some survivors develop heart problems after treatment for children’s cancer and others do not. Therefore, it is important for each survivor treated with anthracyclines or chest radiation to have regular medical check-ups so that if a problem with the heart develops, it can be detected and treated early.

Symptoms of Heart Problems

• Shortness of breath
• Dizziness
• Lightheadedness, near fainting, or fainting
• Severe fatigue preventing exercise or normal play
• Chest pain that feels like a heavy pressure or fullness and travels to the arm, chin or face.
• Sweating, nausea, or shortness of breath with chest pain
• Sharp piercing pain in the center or the left side of the chest (often worsens with taking a deep breath)
• Very swollen feet or ankles (so swollen that if a finger is pressed firmly on the area for a few seconds it leaves an indentation)
• Cough and wheezing that doesn’t go away
• Periods of heart racing or throbbing
• Periods of irregular heartbeat (feeling of the heart skipping beats)

Conditions and Activities that Worsen Heart Problems

A heart affected by anthracyclines and chest radiation may not be able to handle the stress of certain conditions that dramatically increase heart rate, blood pressure, or volume of blood in the circulatory system.

If cancer treatment included medicines that can affect heart function, patients need to work with their doctor in order to ensure reduced stress to the heart. Some drugs may cause stress to the circulatory system, including cocaine, diet pills, ephedra, mahuang, and performance-enhancing drugs. These types of drugs have been associated with worsening of heart function and even death in children’s cancer survivors who received anthracycline chemotherapy.

Exercise is usually good for the heart, but some types of exercise are particularly stressful to the heart. To be safe, survivors treated with anthracyclines or chest radiation therapy should check with their healthcare provider before beginning any exercise program. Those who choose to engage in strenuous or varsity team sports should discuss appropriate guidelines and a plan for ongoing monitoring with their doctor.

Monitoring for Heart Problems

Anyone treated with anthracycline chemotherapy or chest radiation for children’s cancer should have a yearly check-up that should include specific evaluation of any symptoms relating to the heart. In addition, an electrocardiogram (ECG, EKG) should be done at the time the survivor enters long-term follow-up (usually about 5 years from diagnosis or 2 years from completion of therapy). An echocardiogram or Multi- Gated Acquisition (MUGA) scan is also recommended at the first long-term follow-up visit, then according to the following schedule (or as recommended by the healthcare provider):

Schedule for Echocardiogram or MUGA Scans

Age at Treament*	Chest Radiation	Total anthracycline dose**	Recommended frequency of ECHO or MUGA
< 1 year	Yes	Any	Every year
	No	< 200 mg/m²	Every 2 years
		≥ 200 mg/m²	Every year
1 to 4 years old	Yes	Any	Every year
	No	< 100 mg/m²	Every 5 years
		≥ 100 to < 300 mg/m²	Every 2 years
		≥ 300 mg/m²	Every year
≥ 5 years old	Yes	< 300 mg/m²	Every 2 years
		≥ 300 mg/m²	Every year
	No	< 200 mg/m²	Every 5 years
		≥ 200 to <300><300 mg/m²="mg/m²" </td="</td" />300	Every 2 years
		≥ 300 mg/m²	Every year

*Age at first treatment with anthracycline or chest radiation (whichever was given first). **Based on total doses if doxorubicin/daunorubicin or the equivalent doses of other anthracyclines.

Survivors who received radiation at a dose of 40 Gy (4000 cGy) or higher to the heart or surrounding tissues or radiation at a dose of 30 Gy (3000 cGy) or higher plus anthracycline chemotherapy should do a stress test 5 to 10 years following radiation, then as recommended by a cardiologist.

Survivors who received radiation to the heart or surrounding tissues should also have a blood test to check for other cardiac risk factors (lipid profile and fasting glucose) every 3 to 5 years.

Additional evaluation by a cardiologist is recommended for female survivors who are pregnant or planning pregnancy, and received any of the following therapies:

• Anthracycline chemotherapy at a dose of 300 mg/m2 or more
• Radiation at a dose of 30 Gy (3000 cGy) or higher to the heart or surrounding tissues
• Radiation at any dose to the heart or surrounding tissues, if the patient also received anthracycline chemotherapy
• Total body irradiation (TBI) plus high doses of cyclophosphamide (Cytoxan) prior to bone marrow or stem cell transplant
• Total body irradiation (TBI) plus anthracycline chemotherapy

Common Heart Tests
An electrocardiogram (EKG) is used to evaluate heart rate and rhythm. Electrodes (small sticky patches that conduct electricity) are placed on the chest, arms, and legs. Wires are attached to the electrodes and the electrical impulses of the heart are recorded.

An echocardiogram (heart ultrasound) is used to test the muscle function of the heart and determine how well it pumps. The patient lies on a table and a technician applies conductive jelly to the chest. Then, a transducer (handheld device that emits the ultrasound waves) is placed on the chest to obtain different views of the heart. The echocardiogram technician will apply slight pressure on the transducer, to the chest. The test results are recorded for the doctor to review. Many measurements are done during this test to help find out if the heart muscle is pumping blood well. The ultrasound test also looks at the valves of the heart to check that they open and close normally. Electrodes are usually placed on the chest to monitor the heart’s electrical impulses during the test.

A cardiac stress test measures heart function during periods when the heart is working hard. During this test, a person’s heart and blood pressure are monitored while walking on a treadmill.

If a Heart Problem is Detected

The healthcare provider will advise patients about any follow-up care needed. Sometimes, a referral to a cardiologist (heart specialist) is needed for additional evaluation and/or treatment with medications.

Preventing Heart Problems

With increasing age, the risk of certain types of heart disease (such as heart attacks and hardening of the arteries) also increases. Factors that may increase the risk of heart problems include smoking, being overweight, eating a high-fat diet, and not exercising. Medical conditions that increase the risk include diabetes, high blood pressure, and high blood cholesterol. Individuals can reduce their risk of heart problems by:

• Not smoking (or quitting if currently smoking).
• Maintaining a healthy body weight.
• Limiting the fat in the diet to no more than 30% of calories.
• Exercising moderately for at least 30 minutes on most days of the week.

If someone has diabetes, high blood pressure, or high blood cholesterol, they should try to keep these under good control with diet or medication as recommended by their healthcare provider. Any symptoms of heart problems should be promptly reported to a healthcare provider.