Chemotherapy can indeed cause heart damage, a condition known as cardiotoxicity, which is a significant concern in cancer treatment. This damage can range from subtle changes in heart function to severe heart failure, depending on the type of chemotherapy drugs used, the dosage, and individual patient factors.
One of the most well-known chemotherapy agents linked to heart damage is doxorubicin, an anthracycline drug widely used to treat various cancers such as breast cancer and lymphomas. Doxorubicin can cause damage to the heart muscle cells through several mechanisms, including mitochondrial dysfunction, stress on the cell’s protein-folding machinery (endoplasmic reticulum stress), disruption of calcium balance, and direct DNA damage. These effects lead to the death of heart muscle cells and the development of fibrosis, which is scarring of the heart tissue. This fibrosis impairs the heart’s ability to pump effectively, often in a dose-dependent and irreversible manner. The risk of heart failure increases with higher cumulative doses of doxorubicin, with significant risk observed at doses above 400 mg/m² and becoming more pronounced at doses of 550 mg/m² and 700 mg/m².
Other chemotherapy drugs, such as trastuzumab used in HER2-positive breast cancer, can also contribute to heart damage, especially when combined with anthracyclines. The combination therapy increases the incidence of adverse cardiac events over time, with nearly a third of patients experiencing cardiac issues within three years of treatment. The heart damage from these drugs can manifest as a decline in the left ventricular ejection fraction (LVEF), which is a measure of how well the heart pumps blood.
The timing of chemotherapy administration may also influence the risk of heart damage. Observational studies suggest that patients receiving anthracycline chemotherapy in the afternoon have a higher risk of developing permanent heart damage and heart failure compared to those treated in the morning. This finding points to the possibility that the body’s circadian rhythms affect how chemotherapy drugs impact the heart, although further research is needed to confirm this and to develop optimized treatment schedules.
Detecting chemotherapy-induced heart damage early is crucial. Biomarkers such as troponins and natriuretic peptides (NPs) are valuable tools for this purpose. Troponins are proteins released into the blood when heart muscle cells are injured and can indicate early myocardial injury during chemotherapy. Elevated troponin levels during treatment are strongly associated with a higher risk of cardiotoxicity and subsequent heart dysfunction. Natriuretic peptides, on the other hand, are more reflective of later-stage heart damage and heart failure. Monitoring these biomarkers helps clinicians identify patients at risk and adjust treatment accordingly.
The mechanisms behind chemotherapy-induced heart damage are complex and involve multiple pathways. For anthracyclines, the damage includes ferroptosis (a form of cell death linked to iron and oxidative stress), endothelial damage (affecting the blood vessels), apoptosis (programmed cell death), fibrosis, and inflammation mediated by specific molecular pathways such as NF-kB. These processes collectively impair the heart’s structure and function.
Because chemotherapy-induced cardiotoxicity can limit cancer treatment options and negatively affect patient outcomes, cardioprotective strategies are an active area of research. Traditional cardiovascular drugs like beta-blockers and inhibitors of the renin-angiotensin-aldosterone system (RAAS) have been used with some success, but their effectiveness is limited. New approaches, including the use of drugs like SGLT2 inhibitors, are being explored for their potential to prevent or reduce heart damage during chemotherapy.
In clinical practice, patients receiving potentially cardiotoxic chemotherapy undergo regular monitoring through blood tests, electrocardiograms, and echocardiography to assess heart function and detect early signs of damage. Adjustments to chemotherapy regimens, timing of administration, and the introduction of cardioprotective agents are strategies employed to minimize the risk.
Overall, while chemotherapy is