Use of the wrong corrected QT interval (QTc) formula is associated with inappropriate changes in the clinical management of patients with cancer, according to a recent study published in JAMA Oncology.1
Specifically, use of the Bazett formula resulted in higher QTc values that were associated with a 3-fold increase in grade 3 Common Terminology Criteria for Adverse Events (CTCAE) toxic effects, compared with other commonly used formulas.
“Many different formulae are available to calculate QTc. For example, the Bazett, Fridericia, and Framingham formulae are frequently used in clinical practice without a uniform standard,” the researchers explained. “The Bazett formula predominates because many automated electrocardiogram (ECG) reporting software packages default to this formula, often without clinicians’ awareness.… The detrimental effect of using the Bazett formula to inform treatment decisions in oncology has not been fully explored.”
In this retrospective study, the researchers used data from January 2020 to April 2020 from adult patients seen at the University of North Carolina (UNC) Cancer Hospital who had an ECG performed. During this time, almost 20,000 ECGs were performed for 6881 adult patients (44.4% were women).
The percentage of ECGs that were grade 3 QTc prolongation differed by the formula used. For all patients, the percentage was 1.8% for Framingham, 2.7% for Fridericia, and 9.0% for Bazett.
The Bazett formula resulted in a median QTc value of 26.4 milliseconds higher than Fridericia and 27.8 milliseconds higher than Framingham.
Using the Bazett formula, 1786 ECGs were classified as grade 3. Of these, 81.0% were classified as grade 2 or lower by Fridericia or Framingham.
“We initially discovered this problem while treating a patient with acute promyelocytic leukemia with arsenic trioxide, a drug known to cause QT prolongation. We realized that there was inconsistent guidance about how to assess the QT interval with this drug and what values should lead to dose reductions,” senior study author Joshua F. Zeidner, MD, an associate professor of medicine and chief of leukemia research at UNC Lineberger, said in a press release.2
“The clinical protocol that ultimately led to the approval of this drug used a very specific QT formula — Framingham — and we were using a different formula — Bazett — to guide our treatment decisions. Prior to this discovery, most of us were not aware that there were multiple formulas available for corrected QT intervals. The findings from this study have been practice-changing as we no longer recommend the Bazett formula for clinical guidance.”2
For their next steps, the researchers are considering conducting a study evaluating oncologists’ and pharmacists’ awareness of the different QT prolongation formulas and their impact as this would help the researchers better grasp the magnitude of the issue. Primarily, though, the researchers want to advocate for an understanding of the effect of formula choice on outcomes and to advocate for standardization when assessing oncology patients.
Disclosures: This research was supported by National Center for Advancing Translational Sciences. The study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
1. Richardson DR, Parish C, Tan X, et al. Association of QTc formula with the clinical management of patients with cancer. JAMA Oncol. Published online September 22, 2022. doi:10.1001/jamaoncol.2022.4194.
2. UNC Lineberger Comprehensive Cancer Center. Accurate assessment of heart rhythm can optimize chemotherapy use [news release]. September 22, 2022. Accessed September 29, 2022. https://www.eurekalert.org/news-releases/965554