Prevalence of discordant QTc values among cancer patients by the Bazett, Fridericia, and Framingham formulae: Evidence for a standardized approach.

Abstract

6575 Background: Many chemotherapies have the potential to prolong the QT interval, requiring monitoring of the corrected QT (QTc) to prevent life-threatening arrhythmias. Most clinical guidelines recommend adjusting/holding chemotherapy with Grade 3 or higher toxicity by CTCAE (QTc≥500). Several formulae are used for QTc monitoring including Bazett, Fridericia, and Framingham. The most commonly used formula, Bazett, is well-documented to result in inappropriately high QTc values although the potential impact of this overcorrection on cancer treatment is unknown. We aimed to describe the prevalence of QTc prolongation among cancer patients and the effects on CTCAE adverse event grading by various QTc formulae to determine the potential impact on clinical management. Methods: We performed a single-center retrospective analysis of QT values from electrocardiograms (ECGs) collected January 2010-April 2020 and evaluated associations between QTc values, medications, and patient characteristics. QTc prolonging agents were determined by FDA package insert and cross-referenced with CredibleMeds.org. Results: 20,017 ECGs were evaluated. 18.6% (3,730) met ACC/ACCF/HRS criteria for prolonged QTc by ≥1 QT correction formula (either Bazett, Fridericia, or Framingham). 7.5% (1,494) were prolonged with all three formulae, and 8.6% (1,635) were prolonged only with Bazett. The CTCAE classification using the Bazett formula differed from both Fridericia and Framingham in 37.9% (7,583) of the ECGs. In contrast, Fridericia and Framingham formulae resulted in the same CTCAE classification in 94.5% (18,912). Of 1,789 ECGs classified as Grade 3 toxicity by Bazett, 72.0% (1,288, 6.4% of all ECGs) were classified as Grade 2 or less by both Fridericia and Framingham. 12.0% (2,340) of all ECGs were taken from patients (n = 421) on 24 different QT-prolonging chemotherapies. In 38.8% (909) of the ECGs, the CTCAE classification using the Bazett formula differed from both Fridericia and Framingham while use of Fridericia and Framingham formulae resulted in the same classification in 93.0% (2,176) of the ECGs. Of 293 ECGs classified as Grade 3 toxicity by Bazett, 65.2% (191) were classified as Grade 2 or less by both Fridericia and Framingham. Conclusions: To our knowledge, this is the largest analysis of discrepancies between different QTc formulae in patients receiving chemotherapy. These findings demonstrate an unacceptably high rate of discordance between formulae. Discordant data can lead to inconsistent clinical management and adverse event grading underscoring the urgent need to standardize QTc monitoring and reporting. These findings support the discontinuation of the routine use of the Bazett correction formula among cancer patients as CTCAE Grade 3 reporting from the Bazett formula is unreliable in over 65% of cases.