Chemotherapy Cardiotoxicity Attenuation
Heart damage from cancer treatment is a serious concern that can limit lifesaving therapies, but several strategies and medications show promise in protecting the heart while patients receive chemotherapy.
Table of contents
- What Is Chemotherapy-Induced Cardiotoxicity?
- How Chemotherapy Damages the Heart
- Detecting Heart Damage
- Medications That Protect the Heart
- Other Prevention Approaches
What Is Chemotherapy-Induced Cardiotoxicity?
Cardiotoxicity refers to heart damage that arises from cancer treatments or drugs. This condition has become an increasingly important issue as cancer survival rates improve, with more people living longer after treatment[1]. While chemotherapy has shown great progress over the past two decades, the cardiovascular side effects of modern cancer drugs have also proven to be a growing problem, even appearing years after treatment ends[1].
This heart damage can develop in anyone who has had cancer treatment, but it is more likely in people who have taken specific drugs or received radiation therapy to the chest[2]. Studies estimate that up to 20% of adults who received cancer treatment as children may develop heart problems, with 7% to 10% experiencing cardiomyopathy (a heart muscle condition that makes it harder for the heart to pump blood) or heart failure[2].
The clinical signs of cardiotoxicity cover a broad range of disorders, from mild temporary irregular heartbeats to potentially deadly conditions such as heart attacks and cardiomyopathy[1]. Symptoms may include chest pain, dizziness, heart palpitations, shortness of breath, and swelling in the legs[2]. The development of these heart problems, even when they produce no symptoms, not only has a negative impact on a patient’s heart health outlook but also severely limits treatment options[1].
How Chemotherapy Damages the Heart
The most studied chemotherapy drugs associated with adverse heart effects are anthracyclines (such as Doxorubicin), which are used to treat many adult cancers including breast cancer, sarcoma, lymphoma, and gynecological cancer. These drugs currently appear in more than 50% of treatment plans and contribute to overall survival rates exceeding 75%[1]. Anthracyclines are responsible for both early and late cardiotoxicity, particularly heart failure, and the risk is related to the total amount of the drug received[9].
One of the most widely accepted explanations for chemotherapy-induced cardiotoxicity involves the creation of oxidative stress, which occurs when harmful molecules called reactive oxygen species (ROS) damage cells[3]. Understanding these molecular mechanisms of chemotherapy-induced cardiotoxicity is key to developing effective prevention strategies and improved treatment plans[3].
Other chemotherapy drugs can also cause heart damage. Trastuzumab (Herceptin), a targeted therapy drug commonly used to treat breast cancer and stomach cancer, has been noted to cause a significant decline in heart pumping function in 7.1% to 18.6% of patients. When combined with an anthracycline and cyclophosphamide, heart dysfunction can occur in up to 27% of patients[4].
Detecting Heart Damage
Healthcare providers diagnose cardiotoxicity by measuring how well the heart pumps blood using a measurement called left ventricular ejection fraction (LVEF), which shows how much blood pumps out of the lower left heart chamber each time the heart contracts[2]. Cancer therapy-related cardiac dysfunction is broadly defined as a decrease in LVEF of at least 10% to less than 50%[4].
Several tests are used to measure heart pumping function and valve function. The most common imaging tool is an echocardiogram, which uses electrodes and ultrasound waves to check the heartbeat and view blood flow through the heart. Some experts consider cardiac MRI the gold standard for detecting cardiotoxicity, as it uses magnets, radio waves, and a special computer to create detailed images of the heart’s structures[2].
Screening of cancer patients also includes biomarkers (substances measured in blood tests) such as troponin and natriuretic peptide, which can indicate heart damage[10]. Early identification and management of potential risk factors for cardiovascular side effects appears to contribute to preventing or minimizing cardiotoxicity[10].
Medications That Protect the Heart
Several types of heart medications have been studied to see if they can prevent or reduce chemotherapy-induced heart damage. A comprehensive analysis of 33 randomized controlled trials including 3,285 patients examined the effects of various cardioprotective agents[4].
Spironolactone (an aldosterone receptor antagonist) showed the greatest improvement in heart pumping function, with a mean improvement of 12.80 units compared to control groups. It was also associated with a significant reduction in troponin elevation, a marker of heart damage[4].
Enalapril (an ACE inhibitor, a type of blood pressure medication) demonstrated a mean improvement of 7.62 units in heart function and showed the greatest reduction in BNP (a substance that increases when the heart is stressed). Patients taking enalapril had the lowest risk of developing clinical heart failure compared to those not taking the medication[4].
Nebivolol (a beta-blocker) and statins (cholesterol-lowering medications) also showed significant benefits, with improvements of 7.30 and 6.72 units in heart function, respectively[4]. The analysis confirmed that statins, aldosterone receptor antagonists, ACE inhibitors, and beta-blockers can significantly reduce chemotherapy-induced cardiotoxicity, while ARBs (angiotensin receptor blockers) showed no significant effects[4].
The only medication approved by the United States Food and Drug Administration and European Medicines Agency specifically for preventing anthracycline-related cardiomyopathy is dexrazoxane[13]. This drug is recommended for administration during cancer treatment to limit the heart-damaging effects of anthracycline chemotherapy[13].
However, the routine use of these heart-protecting medications for prevention remains a topic of discussion. The marginal benefits and associated adverse events, particularly with long-term use, mean that routine use of these drugs for heart protection is not currently recommended in all cases[13]. Data regarding optimal dosages, duration of medical therapy, and potential interactions with chemotherapy drugs are still limited[10].
Other Prevention Approaches
Prevention of cardiomyopathy and other types of chemotherapy-related cardiotoxicity involves approaches that minimize exposure to the drug—and therefore its potential heart-damaging effects—alongside initiating cardioprotective drugs to decrease heart injury[9].
Securing heart function is an ongoing challenge for the pharmaceutical industry and the physicians who currently deal with these adverse reactions[1]. Appropriate management should include better detection of patients at risk, the development of preventive strategies, and early treatment of cardiotoxicity when it appears[1].
Risk assessment of cancer patients before starting chemotherapy is crucial, especially in high-risk patients. Those at higher risk include young people, the elderly, people with existing heart conditions, and those receiving additional chemotherapy drugs or chest radiation[10].
Collaboration among oncologists, cardiologists, and cardio-oncologists (specialists in both cancer and heart care) could establish management strategies and approved follow-up protocols for patients with cancer receiving chemotherapy[10]. The growing need to manage patients with drug-related adverse cardiovascular effects has led to the rapid creation and adoption of cardio-oncology, a multidisciplinary science aimed at monitoring, treating, and preventing treatment-related cardiotoxicity[9].
