The current practice of QTc monitoring has the potential to greatly influence the integrity of patient and clinical care, according to a commentary published recently by Benyam Muluneh, PharmD, of the University of North Carolina, Chapel Hill, and colleagues in the Journal of Clinical Oncology.

Based on an observation and formula published by Bazett and Fridericia in 1920, it is now standard to apply a correction formula to the measured QT interval, which measures the combined duration of ventricular depolarization and repolarization.

“Although numerous other formulae have been proposed over the years, the Bazett and Fridericia formulae became incorporated into the computerized ECG [electrocardiogram] interpretation algorithms and remain in widespread use today,” Muluneh and colleagues wrote. “Important shortcomings of both formulae have been recognized for years, most notably that the Bazett formula has a strong positive correlation with heart rate that demonstrably leads to substantially higher QTc values than other methods.”

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A study comparing the Bazet formulae with other calculations showed that Bazett performed the worst for QTc assessment “because of significant over- and underestimation of QTc during fast and slow heart rates, respectively”.

“These important findings suggest that the Bazett formula does not provide reliable assessment of pro-arrhythmic risk, overestimates the number of patients with potentially dangerous QTc prolongation, and can thereby misinform clinical decisions,” they wrote.

In recent years, the FDA has approved 5 chemotherapy drugs that require periodic QTc monitoring and have specific dose-reduction or holding recommendations based on QT measurement. Although the FDA recommends against the use of the Bazett formula, only 1 of these 5 drugs’ labels has a specific recommendation for which formula should be used for QTc monitoring.

In addition, despite recommendations from the FDA and other medical organizations, Bazett is still the default formula in many ECG systems, and its use could result in the unnecessary hold of potentially curative chemotherapy.

“We are concerned that ongoing widespread and often unrecognized use of the Bazett formula to guide therapeutic decision making has compromised the care of patients with cancer by spuriously limiting access to optimal chemotherapy,” Muluneh and colleagues wrote. They added that while QT prolongation heightens the risk for ventricular arrhythmias, “the Bazett formula systematically overestimates that risk compared with both the Fridericia and the Framingham corrections.”

As a solution, they recommended the use of only 1 uniform QTc formula to “minimize confusion and foster transparency.”

Reference

Muluneh B, Richardson DR, Hicks C, et al. Trials and tribulations of correlated QT interval monitoring in oncology: rationale for a practice-changing standardized approach [published online July 16, 2019].  J Clin Oncol. doi: 10.1200/JCO.19.00922