Which QTc calculation (Hodges, Bezet, etc.) best estimates the risk of life-threatening arrhythmias such as TdP?

Comment by InpharmD Researcher

There does not appear to be a consensus on which QT correction calculation best estimates the risk of life-threatening arrhythmias; however, some formulas in general may better predict mortality than others. Observational data have found the Fridericia and Framingham formulas provide the most accurate rate correction, while the Bazette correction formula may lack in providing accurate rate correction, indicating the potential for significant over- and underestimation of QTc at high or low heart rates, respectively. The Fridericia, Framingham, and Hodges formulas have all been shown to be significant predictors of mortality, while the Bazette formula has not. Each formula has different strengths and limitations and may be more appropriate for specific scenarios (see Table 1).

Background

A 2020 review discussing the measurement of QT interval prolongation notes that while several correctional formulas exist, none have proven superior. An algorithm to determine which formula to use is also provided. If a patient does not show atrial fibrillation, and the QRS duration is broad (> 120 ms or 3 small squares on standard ECG paper), it is suggested to consider the modified Bogossian formula (QTc= QT - 0.5x [QRS duration]). If the QRS duration is narrow (<120 ms or 3 small squares on standard ECG paper) and the heart rate is <50, it is recommended to use the nomogram provided by the authors (nomogram figure pictured in the article) or the Fridericia formula. For patients with narrow QRS duration and heart rate between 50 to 70, it is suggested to use the nomogram, Fridericia or Bazett formula. Finally, for patients with a narrow QRS duration and heart rate > 70, it is suggested to use the nomogram. See Table 1 for a summary of methods for correction of the QT interval with their respective strengths, limitations, and recommendations for use. [1]

The nomogram described in the article has been developed so the heart rate and the uncorrected QT can be plotted. A point plotted above a pre-defined line is associated with a higher risk of torsades de pointes (TdP). The nomogram, if available, is said to be the simplest method of QT interval interpretation, as a specific formula does not need to be applied. Compared to the Bazette formula, the nomogram has been shown to have equivalent sensitivity and specificity in a systematic review of 129 cases of TdP and was less likely to generate false positive results in two retrospective studies. The nomogram, however, lacks robust prospective data supporting its use; thus, it is not referenced in major guidelines. The nomogram can be found in Figure 3 within the following link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080915/. [1]

A retrospective study aimed to determine which QT correction formula to use in an automated-QT monitoring algorithm for the electronic medical record. All electrocardiograms (ECGs) in patients > 18 years with sinus rhythm, normal QRS duration, and rate <90 beats/minute at a single center in Belgium during a 2-month period were included. The Bazette, Fridericia, Framingham, Hodges, and Rautaharju formulas were used to perform QT correction. A total of 6,609 patients were included (average heart rate 68.8 beats/minute). Using a population‐based approach, the relation between QTc and RR interval was determined using scatterplots for QTc/RR pairs per subject. QTc/RR linear regression slopes were calculated with the template: QTc=BxRR+intercept, and given that optimal QTc correction should be independent of the RR interval, the slope of the linear regression (B) and R^2 should be zero. The QTc/RR analysis identified the Fridericia and Framingham correction formulas as the best rate correction in this population, with slopes of 0.004 and −0.005, respectively. Bazzett’s correction formula, with a slope of -0.071, performed the worst, indicating the potential for significant over- and underestimation of QTc at high or low heart rates, respectively. Based on multivariate Cox regression, which included age, heart rate, and prolonged QTc, Framingham (hazard ratio [HR] 7.31; 95% confidence interval [CI] 4.10 to 13.05) and Fridericia (HR 5.95; 95% CI 3.34 to 10.60) were found to be significantly better predictors of 30-day all-cause mortality than Bazett (HR 4.49; 95% CI 2.31 to 8.74). Based on these results, it was suggested that the Fridericia formula may be an appropriate clinical standard for replacing the Bazett formula for hospital-based QT monitoring. [2]

Another retrospective study that evaluated four formulas of QT interval correction in individuals with sinus tachycardia included 6,723 patients without a history of heart failure with a baseline sinus rate ≥ 100 beats/minute. QT prolongation was diagnosed in 39% of the cohort using the Bazett formula, 6.2% using the Fridericia formula, 3.7% using the Framingham formula, and 8.7% using the Hodges formula. Only the Hodges formula was determined to be an independent predictor for death across the range of QT values (highest tertile HR 1.26; 95% CI 1.03 to 1.55). Despite all formulas showing an association between QTc values and cardiovascular events, only the Hodges formula was able to identify a significant number of individuals with tachycardia that are at higher risk for all-cause mortality. Additionally, it is suggested that the Bazett formula may overestimate the number of patients with a prolonged QT and was not associated with mortality. [3]

References:

[1] Indraratna P, Tardo D, Delves M, Szirt R, Ng B. Measurement and Management of QT Interval Prolongation for General Physicians. J Gen Intern Med. 2020;35(3):865-873. doi:10.1007/s11606-019-05477-7
[2] Vandenberk B, Vandael E, Robyns T, et al. Which QT Correction Formulae to Use for QT Monitoring? [published correction appears in J Am Heart Assoc. 2018 Aug 21;7(16):e004252]. J Am Heart Assoc. 2016;5(6):e003264. Published 2016 Jun 17. doi:10.1161/JAHA.116.003264
[3] Patel PJ, Borovskiy Y, Killian A, et al. Optimal QT interval correction formula in sinus tachycardia for identifying cardiovascular and mortality risk: Findings from the Penn Atrial Fibrillation Free study. Heart Rhythm. 2016;13(2):527-535. doi:10.1016/j.hrthm.2015.11.008

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Which QTc calculation (Hodges, Bezet, etc.) best estimates the risk of life-threatening arrhythmias such as TdP?

Please see Table 1 for your response.


 

Formulas for Correction of the QT Interval
Formula Strengths Limitations When to use
Bazett

• Simplest formula

• Widely accepted and used

• Tendency to over-diagnose long QT as it overcorrects at high heart rates and undercorrects at low heart rates • Best used when HR is between 50 and 70 bpm
Fridericia • More accurate than Bazett formula at abnormal heart rates • Tendency to overcorrect at high heart rates (i.e., over-diagnosis of long QT)

• Useful in bradycardic patients (HR < 50 beats/min)

Framingham • Less affected by abnormal heart rate • Complex formula

• In any patient, especially if heart rate is < 50 beats/min or > 70 beats/min

Hodges • Least affected by abnormal heart rate • Complex formula

• In any patient, especially if heart rate is < 50 beats/min or > 70 beats/min

Nomogram • Designed for use with abnormal heart rates

• Needs to be physically or digitally available at point of care

• Difficult to apply to serial testing

• Patients with abnormal heart rates

• Well described in toxicology and overdose

The “Half R-R” method • No calculation required

• Non-quantitative

• If the QT is greater than half the RR interval, it may still be normal

• Cannot be used at HR < 60 beats/min

• Useful as a “screening” test, especially in AF but not as a true diagnostic test.

RR, the R-R interval, measured in seconds; HR, heart rate; AF, atrial fibrillation

 

References:

Adapted from:
Indraratna P, Tardo D, Delves M, Szirt R, Ng B. Measurement and Management of QT Interval Prolongation for General Physicians. J Gen Intern Med. 2020;35(3):865-873. doi:10.1007/s11606-019-05477-7