Cardiovascular Disease: A Common Late Effect of Treatment
Awareness and Vigilance About Checkups and Screenings Is Key
Anyone who has received treatment for Hodgkin Lymphoma needs to understand--and stay up to date on--the late effects that may result. Years later, symptoms can appear that signal a potential health problem.
Cardiovascular disease is in a special category: radiation therapy directed at the chest area combined with the chemotherapy medications that typically are prescribed can lead to damage over time. Effective treatment for Hodgkin Lymphoma often comes with a price, which is why awareness, follow-up and regular screenings are essential
“Patients need these therapies; there is no doubt about that,” says Tochi Okwuosa, DO, Director of the Cardio-Oncology Program at Rush University Medical Center in Chicago and Chair of the Cardio-Oncology Committee for the American Heart Association. “But cancer physicians need to be aware of the cardiovascular side effects, and patients must be aware so they can advocate for themselves and be quick to say: ‘These are the health issues I have; here are the concerns I have about the future.’ And they need to be sure they are seeing the right physician.” (See the list of potential cardiovascular side effects below.)
"Patients need to ask their physician: do you think I should see a cardio-oncologist? An increasing number of hospitals and medical centers have a cardio-oncologist on staff.”
- Tochi Okwuosa, MD
In some cases, the right physician might be a cardio-oncologist--cardiologist who specializes in the cardiac side effects of chemotherapy, targeted therapy and radiation. Their numbers are growing, says Dr. Okwuosa.
“When I completed my cardiology fellowship and began studying cardio-oncology in 2014, there were just a handful of us. In the U.S. today, at least 40 medical centers have cardio-oncology programs. Cardio-oncology is a major topic of discussion. The American College of Cardiology created a council and publications devoted to the field, the American Heart Association followed suit shortly afterwards, and there are now cardio-oncology organizations in Asia, Brazil, Europe and elsewhere.” One important result is an increase in research aimed at refining treatment for Hodgkin Lymphoma, as well as for long-term management.
When should someone consider seeing a cardio-oncologist? “If you are experiencing shortness of breath, leg swelling, chest pain, palpitations, are dizzy, light-headed, having fainting spells or feeling noticeably more tired than usual, you need to see your primary care physician,” says Dr. Okwuosa. “They should review the cancer treatment you received and the tests that need to be performed.
“Most primary care physicians understand this is not their area of expertise. Patients need to ask their physician: do you think I should see a cardio-oncologist? An increasing number of hospitals and medical centers have a cardio-oncologist on staff.”
“The problem with the heart compared with other organs is that the heart has very limited - arguably no ability - to repair itself.”
- Tochi Okwuosa, MD
The Nature of Cardiovascular Damage
Once someone understands how vulnerable the heart and blood vessels are to the most common--and most effective-- treatments for Hodgkin Lymphoma, they know they must watch for symptoms and become vigilant about having the necessary screenings.
“The problem with the heart compared with other organs is that the heart has very limited--arguably no--ability to repair itself,” notes Dr. Okwuosa, who adds that the liver, kidney and brain are more resilient. “Medications and trauma can injure the heart and result in long-term complications. Also, the heart is more easily injured because it depends on the circulation of blood.”
Radiation fibrosis is one problem. The insidious process that occurs in response to radiation exposure causes, over time, sclerosis or hardening in the affected tissue. “We see it in any organ that received radiation, including the heart, lung, kidney and liver,” notes Michael Stubblefield, MD, Director of Cancer Rehabilitation at Kessler Institute for Rehabilitation. “But 70% of those who received radiation to the chest area, as is true of patients who were treated for Hodgkin Lymphoma, will have some degree of cardiac impairment. Valvular disease appears in 43% of affected patients, and arrhythmia in 27%.”
The overall risk of cardiotoxiciy depends on the size of the radiation dose--measured in grays or gy--given and whether or not shielding techniques were used to protect the heart. Those who received radiation in their teens and early 20s are at greater risk for problems. Fortunately, mantle radiation, where the entire chest, including the heart, is treated, is no longer administered; today’s conformal radiation is more precisely focused on the tumor and designed to avoid the heart.
Most physicians are aware that the heart valves can be affected by treatment, but Dr. Okwuosa is quick to mention that radiation can affect the autonomic system--our “fight or flight” system that regulates blood pressure and heart rate. “Because the nerves in that area can be affected, over time patients may experience blood pressures that fluctuate or a heart rate that races enough to become quite uncomfortable. Some patients have problems with fainting spells, which can worsen and become debilitating.”
“It may take 20 years for the damage to become obvious - often heart failure - but many patients will develop symptoms within the first year.”
- Tochi Okwuosa, MD
Chemotherapy is a more complex matter. Certain drugs, specifically the anthracyclines, are known to produce heart damage. “They include doxorubicin [brand name: Adriamycin], which inserts itself into the heart cell and remains there,” says Dr. Okwuosa. “It may take 20 years for the damage to become obvious--often heart failure--but many patients will develop symptoms within the first year. Dosages higher than 250 milligrams are associated with higher risk of cardiotoxicity; lymphoma patients usually receive about 300 milligrams.”
The new targeted therapies, such as immunotherapy, are impressive at treating cancer, but they appear to cause some damage, including heart inflammation (myocarditis and/or pericarditis), she notes. “We are looking carefully at the late effects of these newer medications.”
Regular Tests and Screenings Are Essential
It is very important that patients keep their cardiac risk factors under control. This begins with committing to a healthy lifestyle through diet, exercise, not smoking and maintaining the right weight. Patients should monitor their blood pressure and have their cholesterol levels checked annually. If one has a history of heart disease in the family, being attentive to cardiac risk factors is even more important.
In addition to maintaining good health, Dr. Okwuosa suggests the following screenings to those who receive treatment for Hodgkin Lymphoma:
Before treatment: A baseline electrocardiogram (EKG) should be performed, as it will provide a clear picture of the heart’s electrical activity.
After treatment: An EKG and echocardiogram (ECHO), which uses ultrasound to show how the heart’s chambers and valves are pumping blood through the heart, should be performed.
Annually: An EKG should be performed to screen for signs of heart block - when the electrical signal that controls the heartbeat is partially or completely blocked - or an arrhythmia, a condition where the heart beats irregularly, either too fast or too slow.
Every three to five years: An echo and cardiac stress test should be performed to check for coronary artery disease, valvular heart disease - where one of the heart’s valves is damaged or disease - and pericarditis, where the pericardium - the thin membrane that surrounds the heart - becomes swollen and irritated.
Cardiovascular Conditions Associated with Hodgkin Lymphoma Treatment
Those who have been treated for Hodgkin Lymphoma need to watch for symptoms that may signal one of the following conditions:
• Heart failure: Formerly known as congestive heart failure, this occurs when the heart muscle pumps blood inadequately. As a result, fluid builds up in the heart, forcing it to pump less efficiently.
Symptoms include shortness of breath; weakness and fatigue; swelling in the legs, ankles and feet; irregular heartbeat; weight gain due to fluid retention; lack of appetite and nausea; and chest pain.
• Valve disease: This occurs when one or more of the four heart valves (aortic, mitral, tricuspid, pulmonary) do not work properly. Radiation and chemotherapy can each lead to damage, where the heart valves become scarred, stiff or sclerotic, a condition known as valvular stenosis. Because the valves cannot open and close properly, the result may be leaky valves or regurgitation, where blood flows back into the heart instead of away from it.
Symptoms include shortness of breath, weakness and dizziness, a feeling of pressure or discomfort in the chest, rapid or irregular heartbeat, weight gain and swelling of the ankles, feet or abdomen.
• Arrhythmia: This refers to a disturbance in the heart’s rhythm, where the electrical impulses that coordinate the heartbeat don’t work properly. Radiation to the chest area can damage this electrical system. There are two main types of arrhythmia: tachycardia, a fast heartbeat (a resting heart rate greater than 100 beats/minute), and bradycardia, a slow heartbeat (a resting heart rate of less than 60 beats/minute).
Symptoms include a fluttering in the chest, the feeling of a racing heart, chest pain, shortness of breath, lightheadedness, sweating, fatigue and anxiety.
• Pericarditis: This occurs when the pericardium, the thin membrane that surrounds the heart, becomes swollen or inflamed, which causes the pericardium’s layers to rub against each other, resulting in sharp chest pain. Myopericarditis is a condition where the inflammation becomes significant and spreads to the heart muscle.
Symptoms include chest pain, usually behind the breastbone or the left side of the chest, which often worsens when coughing, lying down or taking a deep breath. Also abdominal or leg swelling, cough, fatigue, low-grade fever and racing heartbeat.
• Pericardial Effusion: This is the buildup of excess fluid in the pericardium, which can put pressure on the heart and affect its ability to work properly.
Symptoms are similar to those of pericarditis and may also include a feeling of fullness in the chest.
• Cardiomyopathy: This is a progressive disease of the heart muscle or myocardium. The heart becomes abnormally enlarged, thickened and/or stiff; as a result, it pumps blood less efficiently, and this causes the heart to work harder than it should. Cardiomyopathy may cause arrhythmia.
Symptoms include shortness of breath, especially after physical exertion; fatigue; and swelling in the abdomen, legs, feet, ankles and veins in the neck.
• Coronary artery disease (CAD) and Atherosclerosis: CAD is a condition where the blood vessels that carry blood to the heart become narrow and hardened due to the build-up of plaque--fatty deposits--in the artery walls. As a result, the heart does not receive enough blood. This process, atherosclerosis, if left untreated, can lead to a significant blockage. Serious damage to the heart may occur and, ultimately, a heart attack or myocardial infarction.
Symptoms include chest pain (angina), often occurring in the middle or left side of the chest, which may not appear until there is a serious blockage. Chest pain may feel like intense pressure or tightness and can be triggered by physical or emotional stress. Other symptoms include shortness of breath and fatigue, especially after extreme activity. Be aware that CAD often develops slowly, over a period of years or decades, and may not be obvious.
Stay Optimistic by Staying Informed
Similar to how progress in curing cancer is on a steady track--between 1991 and 2018, cancer deaths in the U.S. declined by 31%--research is leading to increasingly effective measures aimed at preventing and treating heart disease. Advances in cardiac care are happening all the time; new medications, procedures and surgical techniques are on the horizon.
Individuals who educate themselves, see their primary care physician, cardiologist or cardio-oncologist as needed for checkups and screenings and maintain a healthy lifestyle will feel in control--even optimistic--despite their concerns about late effects that may include cardiovascular disease.