Protein marker predicts possible heart damage after chemotherapy

High levels of troponin I (TNI) protein in the blood helps identify possible heart damage after cancer treatment, according to a report in today’s rapid access issue of Circulation: Journal of the American Heart Association.

The report also suggests that tracking TNI levels can help doctors form a heart disease prevention plan for some chemotherapy patients. “Damage to the heart is one of the most worrisome long-term side effects of high-dose chemotherapy,” said lead author Daniela Cardinale, M.D., deputy director of the cardiology unit at the European Institute of Oncology in Milan, Italy. “Therefore, it is important to identify biochemical markers that might indicate which patients are at greatest risk and how severe their heart disease might be.”

TNI is a protein present exclusively in heart cells. The TNI blood concentration is a well-established marker of heart muscle injury that’s widely used to diagnose and treat heart attacks and other acute coronary syndromes.

“Our study is the first to clearly show, in an adult population, that the risk of cardiac events in cancer patients can be predicted by evaluating the TNI release pattern after chemotherapy,” Cardinale said.

In cancer patients who have had chemotherapy, physicians usually use extensive testing and expensive monitoring equipment to identify which patients may have cardiac toxicity, Cardinale said. These methods “have low sensitivity, poor predictive value and, in some cases, technical limitations. Moreover, these methods identify cardiac damage only when it has already occurred and, in most cases, is not reversible,” she said. “Evaluating TNI value after chemotherapy is an easy, non-invasive, low-cost method that allows us to categorize the risk of cardiac events in cancer patients in the three years following chemotherapy.”

Researchers took blood samples of 703 cancer patients to measure TNI soon after high-dose chemotherapy and one month later. TNI values higher than 0.08 nanograms per milliliter (ng/mL) were considered TNI “positive,” while lower values were TNI “negative.” They found that 145 patients (21 percent) were TNI positive right after chemotherapy, and 63 patients (9 percent) were positive immediately after chemotherapy and one month later.

The researchers found no significant reduction in heart function at the three-year follow-up in patients who were TNI negative. These patients had only a 1 percent incidence of cardiac events, such as heart attacks.

In contrast, the cardiac event incidence was 37 percent among the patients who were TNI positive immediately after chemotherapy and 84 percent among those who remained positive a month later.

Cardinale said the study has several important implications for cancer treatment:

• TNI categorizes heart disease risk early, long before impairment in heart function and symptoms develop, and when many preventive treatments would probably help prevent long-term health effects.
• TNI could assess and monitor the safety and effectiveness of different treatments.
• Heart-protective therapies that might limit or prevent the TNI rise after chemotherapy, and heart treatments that interfere with TNI persistence could improve the future heart health of these patients.

“The results of this study provide a rational need for doctors to use this marker to guide them in their cardiac evaluations and treatments of high-dose chemotherapy patients,” Cardinale said.

Co-authors are: Maria T. Sandri, M.D.; Alessandro Colombo, M.D.; Nicola Colombo, M.D.; Marina Boeri, M.S.; Giuseppina Lamantia, M.D.; Maurizio Civelli, M.D.; Fedro Peccatori, M.D.; Giovanni Martinelli, M.D.; Cesare Fiorentini, M.D.; and Carlo M. Cipolla, M.D.