Using the wrong mathematical formula to assess heart rhythms may cause oncologists to inappropriately stop life-saving chemotherapy, according to research findings from scientists from the United Nations University’s Comprehensive Cancer Center. The researchers report that standardizing mathematical formulas for measuring heart rhythms with an electrocardiogram, and avoiding one commonly used formula, can reduce this unintended consequence.
The results of the study were published in Gamma tumors.
The formulas in this study are based on how the heart system recharges itself after each heartbeat. When reading an electrocardiogram (ECG), the bumps and bulges in the heartbeat, called P through U waves, indicate when the heart is contracting and relaxing. The interval between the onset of the Q wave and the end of the T wave, when it is prolonged, is a major concern for people receiving chemotherapy. When the heart muscle takes a relatively longer time to contract and relax than usual, which is known as QT prolongation, it may increase the risk of developing an abnormal heart rhythm that can lead to sudden cardiac arrest.
Because QT prolongation is a potentially serious side effect, every chemotherapy drug undergoes rigorous QT prolongation testing in its approval process. Many chemotherapy agents that prolong the QT interval today fall into a category known as targeted therapies. As the use of targeted therapies expands, monitoring of QT prolongation becomes more important, especially for the many leukemias often treated with targeted drugs, such as those that were part of this study.
In their study of the different formulas, the researchers discovered that one formula, Bazett’s formula, was associated with a threefold increase in the corrected QT interval compared to other formulas used with tumor patients. Overestimation of the QT interval by the Bazett formula can lead to misleading modification of chemotherapy that could affect clinical care.
Richardson, MD, MSc, assistant professor of medicine at the University of North Carolina Lineberger and corresponding author of the article. “The differences we found between the QT formula were so amazing we didn’t expect the difference when we started this project. It definitely changed the way patients were treated.”
Researchers studied the medical records of 6,881 adult cancer patients who received 24 different types of chemotherapy between 2010 and 2020. The patients were seen at North Carolina Basnatite Cancer Hospital and received nearly 20,000 electrocardiograms.
The investigators found that Bazett’s formula resulted in longer QT intervals than the other two formulas (Framingham and Fridericia) in 40.9% of the ECGs examined; This was concerning because Bazett is the default formula used with many ECG machines.
“We initially discovered this problem while treating a patient with acute myeloid leukemia with arsenic trioxide, a drug known to prolong the QT interval. We realized that there were inconsistent guidelines on how to assess the QT interval with this drug and what values it should lead to Dose cuts “The clinical protocol that eventually led to approval of this drug used a very specific QT formula — Framingham — and we were using a different formula,” senior author Joshua F. Zeidner, MD, assistant professor of medicine and chief of leukemia research at the University of North Carolina-Linberger said. – Bazett – To guide our therapeutic decisions. Prior to this discovery, most of us were unaware that there are many formulas available for QT-corrected intervals. The results of this study have been changed because we no longer recommend the use of Bazett’s formula for clinical guidelines. “
As for their next steps, the researchers are considering a study to assess the awareness of oncologists and pharmacists about different QT-prolongation formulas and their impact as this would help researchers better understand the scale of the problem. Primarily, though, researchers want to advocate for understanding the impact of formula selection on outcomes and to advocate for standardization when evaluating patients with oncology.