Study finds key metabolic changes in patients with chemotherapy-associated cardiotoxicity

BOSTON – More and more patients are being treated successfully for cancer. However, some cancer treatments that are very effective for breast cancer – medications like anthracyclines and trastuzumab – can cause heart dysfunction and 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.

To learn more about the processes that lead to heart toxicity, a team of researchers at Beth Israel Deaconess Medical Center (BIDMC) embarked on 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 heart toxicity at a later time. The study, published in the Journal of Cardiovascular Translational Research, found that metabolites associated with the energy powerhouse of the cell – the mitochondria – changed differently in patients who later developed heart dysfunction compared to those who did not.

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 heart toxicity 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 author Aarti Asnani, MD, Director of the Cardio-Oncology Program at BIDMC. “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 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, Asnani and colleagues will seek to confirm their results in larger patient populations.

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In addition to Asnani, co-authors include Robert Gerszten, MD, Xu Shi, PhD, Laurie Farrell, RN, and Rahul Lall, PhD of BIDMC; Igal Sebag, MD, of Sir Mortimer B. Davis-Jewish General Hospital; Juan Carlos Plana Gomez, MD, of Baylor College of Medicine; and Marielle Scherrer-Crosbie, MD, PhD, of the Hospital of the University of Pennsylvania.

Asnani was supported by a Scholar Award from the Sarnoff Cardiovascular Research Foundation. The project was supported by an investigator-initiated grant from Susan G. Komen and a SPARK grant initiated by Massachusetts General Hospital.

The authors declare no competing interests.

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding.

BIDMC is part of Beth Israel Lahey Health, a new health care system that brings together academic medical centers and teaching hospitals, community and specialty hospitals, more than 4,000 physicians and 35,000 employees in a shared mission to expand access to great care and advance the science and practice of medicine through groundbreaking research and education.