Main metabolic changes observed in patients with cardiac toxicity related to chemotherapy

More and more patients are successfully treated for cancer. However, some highly effective anti-cancer treatments for bad cancer – drugs such as anthracyclines and trastuzumab – can cause heart dysfunction and heart failure. Heart-related side effects may limit the number of cancer treatments to which patients are entitled. There is currently no effective way to predict which patients will develop cardiac dysfunction during or after taking these medications.

To find out more about the processes leading to cardiac toxicity, a team of researchers at the Beth Israel Deaconess Medical Center (BIDMC) has launched a study to determine whether early changes in metabolites related to energy in the blood – measured shortly after chemotherapy – could occur. used to identify patients who have developed cardiac toxicity at a later time. The study, published in the Journal of Translational Cardiovascular Research, found that the metabolites badociated with the cell's energy center – the mitochondria – changed differently in patients who later developed cardiac dysfunction compared to those who did not.

Using blood samples from 38 patients treated with anthracyclines and trastuzumab for bad cancer, the researchers measured 71 energy-related metabolites. They then compared metabolite profiles between patients who developed cardiac toxicity and those who did not, identifying changes in citric acid and aconitic acid that differentiate the two groups of patients.

In particular, citric acid levels increased over time in patients who did not develop cardiac toxicity, but they remained the same or decreased in patients who developed cardiac toxicity. The ability to increase citric acid and related metabolites may be an absent or defective protective response in patients with cardiac toxicity. "

Corresponding Author Aarti Asnani, MD, Director, Cardio-Oncology Program, BIDMC

The researchers also observed changes in the DNA degradation products that differentiated the two groups of patients.

"We hope that these results will eventually lead to the development of biomarkers that can be used to determine which patients have the highest risk of developing cardiac toxicity from chemotherapy," Asnani said. "The identification of high-risk patients could allow us to consider drugs that protect the heart before the start of chemotherapy, or advocate the use of different chemotherapy regimens that are less toxic to the heart." in these patients. "

In their next phase of research to follow this pilot study, Asnani and his colleagues will seek to confirm their findings in larger patient populations.