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Metabolic Changes May Signal Development of Chemotherapy-Associated Cardiotoxicity

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Key Points

  • Levels of citric acid increased over time in patients who did not develop heart toxicity, but they remained the same or decreased in patients who did develop heart toxicity.
  • The ability to augment citric acid and related metabolites may be a protective response that is absent or defective in patients with heart toxicity, said researchers.

To learn more about the processes that lead to chemotherapy-associated cardiotoxicity, a team of researchers at Beth Israel Deaconess Medical Center (BIDMC) conducted a study to investigate whether early changes in energy-related metabolites in the blood—measured shortly after chemotherapy—could be used to identify patients who developed cardiotoxicity at a later time. The study, published by Asnani et al in the Journal of Cardiovascular Translational Research, found that metabolites associated with the mitochondria of the cell changed differently in patients who later developed cardiotoxicity compared to those who did not.

Some treatments used for breast cancer—medications like anthracyclines and trastuzumab—may cause heart dysfunction and can lead to heart failure. Heart-related side effects can limit the amount of cancer therapy that patients are eligible to receive. Currently, there is no effective way of predicting which patients will develop heart dysfunction during or after receiving these medications. 

Methods and Findings

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

“In particular, levels of citric acid increased over time in patients who did not develop heart toxicity, but they remained the same or decreased in patients who did develop heart toxicity,” said corresponding study author Aarti Asnani, MD, Director of the Cardio-Oncology Program at BIDMC, in a press release. “The ability to augment citric acid and related metabolites may be a protective response that is absent or defective in patients with heart toxicity.”

The researchers also observed changes in breakdown products of DNA that differentiated the two groups of patients.
“We hope these findings will ultimately lead to the development of biomarkers that could be used to determine which patients are at the highest risk of developing chemotherapy-related heart toxicity,” said Dr. Asnani. “Identification of high-risk patients could allow us to consider medications that protect the heart before patients begin chemotherapy, or prompt the use of different chemotherapy regimens that are less toxic to the heart in those patients.”

In their next phase of research to follow up on this pilot study, Dr. Asnani and colleagues will seek to confirm their results in larger patient populations.

Disclosure: For full disclosures of the study authors, visit link.springer.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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