Cardiac Toxicity

What is cardiac toxicity (or cardiotoxicity)?

cardiac

Cardiac toxicity is damage to the heart by harmful chemicals. As part of your treatment, you may be given toxins (drugs) to kill cancer cells. A side effect is that the normal cells in and around your heart can also be killed. Besides cell death, other types of cardiac toxicity from cancer treatment include:

  • Cardiomyopathy is when heart muscle becomes weakened, enlarged, thickened, or stiff. This can lead to changes in heart rhythm or to heart failure.
  • Myocarditis is inflammation (swelling) of the heart. This can lead to changes in heart rhythm or heart failure.
  • Pericarditis is inflammation (swelling) of the sac surrounding the heart. This can cause chest pain or heart failure.
  • Acute coronary syndromes are caused by blood vessel damage, which reduces blood flow to the heart. This can cause chest pain or a heart attack (myocardial infarction).
  • Congestive heart failure is when the heart is unable to pump enough blood throughout the body. Chemotherapy can cause mild or severe damage to the heart. If severe, congestive heart failure or other life-threatening problems can occur. A heart transplant may even be needed.

What cancer treatments cause cardiac toxicity?

Chemotherapy

The chemotherapy drugs that most commonly cause heart damage are anthracyclines. Anthracyclines are used to treat many types of cancers. Examples include some types of leukemia, lymphoma, sarcomas as well as bladder, bone, breast, head and neck, kidney, skin, stomach, and other cancers. Anthracyclines include:

  • Daunorubicin (Cerubidine®),
  • Doxorubicin,
  • Doxorubicin liposome injection (Doxil®),
  • Epirubicin (Ellence®),
  • Idarubicin (Idamycin® PFS), and
  • Valrubicin (Valstar®)

In rare cases, cyclophosphamide can damage the heart. This chemotherapy drug is an alkylating agent. It is sometimes used to treat some types of leukemia, lymphoma, myeloma, and sarcomas as well as bone, breast, central nervous system, ovarian, and skin cancers.

Targeted therapy

Targeted therapy drugs that can cause damage to the heart include trastuzumab (Herceptin®), bevacizumab (Avastin®), lapatinib (Tykerb®), sunitinib (Sutent®), and sorafenib (Nexavar®). These drugs are used in a variety of cancer types.

Radiation therapy

Many patients with cancer get radiation therapy to the chest. Examples of cancers that may be treated with radiation include breast cancer, lung cancer, lymphoma, and some childhood cancers. This radiation can damage the blood vessels that bring blood to the heart. Patients who are treated with both anthracyclines and radiation to the chest are at high risk for heart problems. So are patients who are treated with both anthracyclines and trastuzumab.

Who is at increased risk for cardiac toxicity?

Patients who are older, young children, and women have a greater risk for cardiac toxicity. In addition, patients who have other health conditions at the same time as cancer are at increased risk. This is especially true for patients with signs of heart trouble before cancer.

What are the symptoms of cardiac toxicity?

You may not notice any symptoms. Then again, you might have chest pain or notice changes in your heart rhythm. Arrhythmias are health problems with the speed or rhythm of the heartbeat. Atrial fibrillation is the most common type of arrhythmia. It is an abnormal beating of the heart's upper left chamber. It is common not to notice atrial fibrillation.

Your doctor may tell you that you have a decline in LVEF (left ventricular ejection fraction). This means your heart isn't pumping as much blood with each heartbeat as it should. Your treatment will likely be changed if this happens, and you may be started on drugs to help your heart.

If the damage is severe, you may have congestive heart failure. You will probably feel very tired and have trouble breathing. You will first notice the shortness of breath when you are active. Later, you will be short of breath even while resting. Congestive heart failure causes you to gain weight and your ankles to swell. You may also find it uncomfortable to lie on your back.

You might not notice these symptoms until many months or even years after you have completed cancer treatment. Tell your doctor if you any of these symptoms start.

How is cardiac toxicity diagnosed?

Your heart will likely be checked before you start treatment. This will tell your doctor about your baseline (pre-treatment) heart health. Your heart will also be checked regularly during treatment, when starting different treatments, and after you are done with treatment. These are some common tests used to check your heart:

  • Physical exam is a review of your body for signs of disease. During this exam, your doctor may listen to your heart with a stethoscope. If it does not sound normal, there may be damage to your heart.
  • Chest X-ray is a type of imaging test that makes pictures of the insides of your chest. Your doctor can see if your heart looks too big or if fluid is building up in your lungs.
  • Echocardiogram is a type of imaging test that uses ultrasound. Ultrasound bounces sound waves off of organs to make pictures. Your doctor may use an echocardiogram to see your heart in action. Your doctor will be able to see if your heart is pumping enough blood. This is the test used to measure LVEF.
  • ECG (electrocardiogram) is a test that measures the electrical activity of the heart. It lets your doctor see your heart rhythm in detail.
  • MUGA (multi-gated acquisition) scan is a test that injects a radiotracer into your vein. The radiotracer attaches to red blood cells. Next, a special camera is used to see the radiotracer go through your heart. Your doctor can then see how well your heart is pumping. Your doctor can also see how well the blood vessels to the heart are working.
  • Troponin blood tests are done less often. Troponins are proteins found in heart muscle. Troponins are released by dying heart cells and then enter the bloodstream. Troponins may be in your blood even before a decline in LVEF is seen. The use of troponins in the blood to predict heart problems is still being studied.

How can cardiac toxicity be prevented?

Cardiac toxicity can often be prevented by giving less of the cancer drug. Also, you could get lower doses more often instead of larger doses less often. There may be drugs that are less toxic. For example, doxorubicin liposome injection, a liposomal anthracycline, is less toxic than regular doxorubicin.

The problem is balance. You don't want to have more treatment than is needed to treat the disease. Then again, you don't want to undertreat the cancer just to lower the chance of side effects. You should talk to your doctor about the balance of risks and benefits of cardiotoxic treatment for you.

For breast cancer, sometimes dexrazoxane (Zinecard®) is used to prevent or lessen heart damage caused by doxorubicin or epirubicin. It is given right before either drug to protect your heart.

Other drugs are now being tested for prevention of damage to the heart in high-risk patients. These include enalapril, an ACE (angiotensin-converting enzyme) inhibitor, and carvedilol, a beta-blocker.

How is cardiac toxicity treated?

If treatment for cardiac toxicity is started early, it is more likely that serious heart damage will be prevented. If you have heart failure because of cancer treatment, you will be treated like other patients with heart failure. You may be given some combination of these medicines:

  • A diuretic (to control your fluids),
  • An ACE inhibitor (to control your blood pressure),
  • A beta-blocker (to control your blood pressure), or
  • A digitalis drug (to make your heart stronger and to regulate heart rhythm).

In severe cases, a heart transplant may be needed.

Questions for your doctor

  • Do the treatments you are suggesting cause cardiac toxicity?
  • What type of heart damage may occur?
  • Are there safer treatments or treatment schedules we can use?
  • Would these safer choices affect how well my cancer is treated?
  • Is dexrazoxane right for me?
  • How and how often will my heart be checked for problems?
  • Are there any clinical trials that I can join?