What is cardiac toxicity (or cardiotoxicity)?

Cardiac toxicity is damage to the heart by toxins. It can also be called cardiotoxicity. During chemotherapy, you are 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: when the heart muscle becomes weakened, enlarged, thickened, or stiff. This can lead to changes in heart rhythm or heart failure.

• Myocarditis: inflammation (swelling) of the heart. This can lead to changes in heart rhythm or heart failure.

• Pericarditis: inflammation (swelling) of the sac surrounding the heart. This can cause chest pain or heart failure.

• Acute coronary syndromes: reduced blood flow to the heart because of damage to vessels that bring blood to the heart. This can cause chest pain or myocardial infarction (heart attack).

• The damage to the heart can be so mild that you do not notice it. Or the damage can be so severe that the heart becomes weaker and weaker over time. Eventually the heart cannot pump enough blood to the body. This can lead to congestive heart failure and other life-threatening problems. A heart transplant may even be needed.

What cancer treatments cause cardiac toxicity?

The chemotherapy drugs that most commonly cause heart damage are anthracyclines. Anthracyclines are used to treat some types of lymphoma, leukemia, multiple myeloma, and breast cancer. Anthracyclines include:

• Daunorubicin (Cerubidine)

• Doxorubicin (Adriamycin or Rubex)

• Epirubicin (Ellence)

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

Many patients with cancer get radiation therapy to the chest (ex, 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?

Patient who are older, young children, and females have a greater risk for cardiac toxicity. In addition, patients who have other medical 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. The doctor may tell you that you have a decline in left ventricular ejection fraction (LVEF). This means your heart isn’t pumping as much blood with each heartbeat as it should. Your treatment will probably be changed if this happens, and you may be started on drugs to help your heart.

You might notice changes in your heart rhythm (arrhythmias; atrial fibrillation is the most common). Or you might have chest pain.

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 have any of these symptoms.

How is cardiac toxicity diagnosed?

Your heart may be checked before you start treatment with a drug that might damage your heart.  This will tell your doctor about your baseline (starting) heart health. Your heart may also be checked regularly during treatment, when starting different treatments, and after you are done with treatment.

These are some of the more common tests to check your heart:

• Physical 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: Your doctor can see if your heart looks too big or if fluid is building up in your lungs.

• Echocardiogram: Your doctor may use ultrasound to see your heart in action. The doctor will be able to see if the heart is pumping enough blood. This is the test used to measure your left ventricular ejection fraction (LVEF).

• Electrocardiogram (ECG): This test lets the doctor see your heart rhythm in detail.

• Multi-Gated Acquisition (MUGA) scan: For this test, a radioactive substance is injected into your vein. The doctor can then see how well your heart is pumping. The doctor can also see how well the vessels bringing blood to the heart are working.

• Blood test: Less often, your doctor may look for factors called troponins in your blood. These factors are released by heart cells as they die. 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. Or the schedule of the drug can be changed so that you get lower doses more often (rather than larger doses less often). There are also forms of drugs that may be less toxic. For example, liposomal anthracyclines might have less cardiac toxicity than regular anthracyclines.

The problem is balance. You don’t want to have any more treatment than is needed to cure the disease. But you don’t want to lower the chance of cure just to lower the chance of side effects several years later. You should talk to your doctor about the balance of risks and benefits of cardiotoxic drugs for your individual case.

There is a drug called dexrazoxane (Zinecard) that may prevent or lessen the damage to the heart by anthracyclines. It is given at the same time as the cancer drug to protect your heart from damage. However, this drug may affect your chance of being cured, and there may be other risks when you take it. It is usually only given to patients who have the highest risk for cardiac toxicity.

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

How is cardiac toxicity treated?

If you are treated early, more damage to the heart can be prevented and it is more likely that the treatment will succeed.

If you have heart failure because of cancer treatment, you will be treated similarly to 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)

• 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 damage to my heart might occur?

• Are there different, safer treatments or treatment schedules we can use?

• Would these different treatments or schedules affect my chances for a cure?

• Is dexrazoxane right for me?

• How and when will my heart be checked for problems?

Are there any clinical trials in which I can participate?