QT Interval Measurement: Evaluation of Automatic QTc Measurement and New Simple Method to Calculate and Interpret Corrected QT Interval

This observational study was approved by the ethics committee of Cochin Hospital (Paris, France), and each patient gave consent to participate. Patients admitted to the recovery room with nausea or vomiting were enrolled before any administration of antiemetic drug. Exclusion criteria were cardiac arrhythmias or bundle-branch blocks.

For each patient, a standard automatic 12-lead electrocardiogram was obtained (noise filter 0.5–40 Hz), immediately followed by a manual record (noise filter 0.05–100 Hz) at a paper speed of 50 mm/s, both using a Pagewriter M1770 (Hewlett Packard, Andover, MA). Corrected QT interval was calculated by the electrocardiograph (automatic QTc) using the Bazett formula (QTc^b = QT/

).13 

The manual recording was analyzed by a single investigator (B. C.). Briefly, R-R intervals (i.e. , interval between two consecutives R waves) and QT intervals were measured in the chest lead with maximal T-wave amplitude. The end of the T wave was determined as the intersection between the tangent to the steepest down-slope of the T wave and the isoelectric line. Measurements were performed using a digitizing pad (SummaSketch III Professional; Summagraphics, Seymour, CN). Manual QTc^b , using QT and R-R intervals measured manually, was averaged over three to seven consecutive cardiac beats. Interrater reliability was assessed by remeasuring all manual records by one operator.

Both automatic and manual QTc^f were also calculated according to the Fridericia formula (QTc^f = QT/

).14For automatic measures, Fridericia values were calculated using the uncorrected QT and heart rate (converted to R-R [s]= 60/heart rate [beats/min]) printed on the automatic electrocardiographic report. Manual QTc^f was calculated from the same QT and R-R data as those used for the calculation of QTc^b . Manual QTc measurement was considered in this work as the reference method, whichever correction formula was used.

Automatic and manual QTc measurements were analyzed according to Bland-Altman for both QT correction formulae.15They were also compared using a paired t  test. Linear regression between the difference and the mean of the two QT measurement methods was assessed, and the slope of the regression line was compared with zero.

Sensitivity and specificity of the automatic method to differentiate normal and prolonged QTc interval were calculated using the manual measure as the reference. Prolonged QTc interval was defined as QTc greater than 450 ms in women and greater than 440 ms in men.

The correlation coefficient was calculated between R-R and QTc intervals according to either Bazett or Fridericia. These correlation coefficients were taken as measures of the appropriateness to correct QT for heart rate of each formula.16 

Because automatic QTc determination relies on the Bazett formula, we propose a novel parameter, the approximated QTc^f , allowing a simple estimation of QTc^f using the values of uncorrected QT and heart rate routinely printed on the electrocardiographic report. Approximated QTc^f = uncorrected QT × parameter of correction (see Results section and  appendixfor details).

The confidence interval of proportion was calculated using the method of Wilson.17Data are presented as mean ± SD. Ranges in parentheses indicate lower and upper limits of the 95% confidence interval. Analyses were performed using StatView 6.0 software (SAS Institute, Cary, NC). Statistical significance was considered at P < 0.05.

One hundred eight patients were enrolled. Types of surgical procedures were vascular (14%); neurosurgical (18%); ear, nose, and throat (23%); orthopedic (14%); gynecologic (10%); abdominal (5%); and other surgeries (16%). Ninety-two percent of these procedures were performed during general anesthesia. The mean age of the patients was 45 ± 16 yr, and 57% of the patients were women.

Manual QTc^b was 438 ± 32 ms, significantly greater than the automatic QTc^b value (433 ± 28 ms;P < 0.02), with a mean difference in QTc^b of 6 ms (1–10 ms). Limits of agreement between automatic and manual QTc^b interval at the level of 95% were −39 and 51 ms (fig. 1A). The slope of linear regression was 0.16 ± 0.08, significantly different from zero (P < 0.05). This indicates that automatic QTc^b underestimates manual QTc^b as QTc^b increases.

Manual QTc^f was 420 ± 29 ms, significantly lower than manual QTc^b values (438 ± 32 ms; P < 0.001). The mean difference between manual QTc^f and automatic QTc^f measures (413 ± 28 ms) was 7 ms (3–11 ms) (P < 0.001). Lower and upper limits of the 95% confidence interval of the mean difference were −33 and 47 ms, respectively (fig. 1B).

The intraclass correlation coefficient between pairs of QTc interval measurements from manual records was 0.998, and the coefficient of variation was 0.47%.

Manual QTc^b was found to be prolonged in 36% (27–46%) of patients. The sensitivity of the automatic method to differentiate normal and prolonged manual QTc^b interval was 54% (37–70%), and the specificity was 90% (80–95%). The positive and negative predictive values were 75% (55–89%) and 77% (66–86%), respectively.

Manual QTc^f was prolonged in 15% (9–23%) of patients. Sensitivity and specificity of the automatic measurement were 44% (21–69%) and 96% (89–99%), respectively. The positive and negative predictive values were 63% (32–88%) and 91% (83–95%), respectively. The negative predictive value of automatic QTc measurement was greater when using the Fridericia formula than when using the Bazett formula (z = 2.43, P < 0.02).

The mean R-R interval was 798 ± 188 ms (equal to heart rate of 79 ± 17 beats/min). As expected, the linear regression between uncorrected QT interval duration and R-R interval had a significant positive slope (fig. 2A), i.e. , repolarization lengthens as heart rate decreases. A significant correlation was found between QTc^b and R-R intervals (r =−0.398; −0.546 to −0.226; P < 0.001; fig. 2B). Corrected QT interval according to the Fridericia formula was not significantly influenced by heart rate (r = 0.076; −0.115 to 0.261; P = 0.4; fig. 2C). Therefore, the Fridericia formula appropriately corrected QT for heart rate in the study population. Hence, manual QTc^f will be considered below as the reference value.

The analysis of various thresholds of automatic QTc^b to identify prolonged manual QTc^f using a receiver operator characteristic curve permits identification of the value of 430 ms where sensitivity was 100% (81–100%) and specificity was 53% (43–63%).

Values of the parameter of correction to calculate “approximated QTc^f ” are presented in table 1for heart rates between 40 and 125 beats/min. In our patients, approximation of QTc^f was not significantly different from automatic QTc^f (mean difference, 1.8 ms; P = 0.6). Ninety percent of our patients had a heart rate between 50 and 100 beats/min; in this range, the maximal error between approximated QTc^f and actual QTc^f was 11 ms.

To comply with threshold value used in the E14 guideline,∥prolonged QTc interval will be defined below as a manual QTc^f of 450 ms or greater, irrespective of sex. Automatic QTc^b was 430 ms or greater in 58 patients. Approximated QTc^f was calculated in these patients (fig. 3). In 31 of them (53%), approximated QTc^f was below 430 ms, confirmed by a normal manual QTc^f in all of them. Twenty-seven patients (25%) had both QTc^b and approximated QTc^f of 430 ms or greater. Among these 27 patients, manual assessment of QTc^f was normal (< 450 ms) in 15 patients (55%) and above 450 ms in 12 patients (45%).

We found that electrocardiographic device–generated QTc interval measurement, which uses the Bazett formula by default, is inappropriate to identify all patients with prolonged QTc interval in part because of inadequate QT interval correction. However, automatic uncorrected QT and R-R measurements can be used to generate QTc according to the Fridericia formula.

Ideally, the threshold between normal and prolonged QT interval should be based on an assessment of the arrhythmic risk related to QT/QTc interval duration.5To date, these studies requiring a very large number of patients are lacking in the field of anesthesiology. However, given the high prevalence of prolonged QT interval in our patients, using standard definitions, and the extremely low incidence of arrhythmic events, the standard threshold might be defective in postanesthesia patients.18,19 

QT interval monitoring is difficult because neither manual nor automatic measurements ideally reflect the duration of ventricular repolarization. In our study, we chose manual high-precision measurement performed by a trained reader as the reference method in accordance with guidelines∥and consensus on the subject.5Compared with this method, automatic measures did not detect prolonged QT interval in almost 50% of patients. Because electrocardiograph manufacturers use a similar algorithm for waveform measurements, it is unlikely that our results were significantly influenced by the chosen device. However, it would be impractical and time-consuming to assess QTc^f interval manually in all patients. Furthermore, Viskin et al.  1recently found that less than 40% of physicians, even among cardiologists, reliably recognize QT prolongation on a standard electrocardiogram. Automatic measurements may be useful to identify patients in whom manual measurement is justified to confirm prolonged QT interval.

No consensus exists on the way to correct QT interval to account for heart rate changes.9Using more than 10,000 electrocardiograms, Luo et al.  12demonstrated that the threshold for normal QT interval is greatly influenced by the correction formula used. We found significant correlation between QTc^b and R-R values, indicating that the Bazett formula does not satisfactorily correct QT interval duration in our patients.16Moreover, as shown in figure 2, the Bazett formula overcorrects QT at high heart rates, i.e. , QTc^b is falsely prolonged as heart rate increases above 60 beats/min. This probably accounted in part for the high prevalence of prolonged QT interval in our patients. To the best of our knowledge, this is the first time that the Bazett correction has been evaluated in the postoperative period. The choice of the postoperative period when heart rate tends to be high may, however, have disadvantaged the Bazett correction. Nevertheless, it is now clearly demonstrated that the Fridericia formula, although still imperfect, corrects QT interval better than does the Bazett formula as heart rate diverges from 60 beats/min.9,10,16Therefore, the Fridericia formula seems to be a proper QT interval correction in the postoperative setting.

Our results indicate that it is not possible to rely solely on automatic QTc^b interval to identify all patients with prolonged QTc interval, because automatic QTc^b has a low sensitivity. To help clinicians identify patients with prolonged QT interval in the postoperative setting, we built a multiple-step approach using a combination of automatic and manual QT interval determination (fig. 3). However, we cannot exclude that the effect of anesthesia on cardiac repolarization in particular by changes in plasma electrolytes or residual volatile anesthetics effects may have affected our results.20 

The value of QTc^b automatically calculated by the electrocardiographic device was first considered. Patients with automatic QTc^b of less than 430 ms were at very low risk of having a prolonged QT interval. The false-negative rate was at most 7% in the studied population (upper limit of the 95% confidence interval of the negative predictive error). No further investigation seems to be justified in these patients. Patients with automatic QTc^b greater than 430 ms may have either normal or prolonged manual QTc^f . In these patients, calculation of QTc^f should be determined to reduce the number of falsely prolonged QT intervals. We propose a new way to calculate QTc^f that is both easily memorizable and calculable. The heart rate for which no correction is needed is, by definition, 60 beats/min. For each increase of 10 beats/min from 60 beats/min, the correction factor increases by one multiple of 5%, i.e. , 1 × 5 = 5%, 2 × 5 = 10%, 3 × 5 = 15%, and so forth, and inversely when heart rate is below 60 (fig. 4). Finally, the QTc^f is easily calculated by adding or subtracting a multiple of 5% of uncorrected QT interval (easily calculable as QT divided by 10 and then by 2). Without any manual QT interval measurement, calculation of approximated QTc^f would have identified more than one half (54%) of falsely prolonged automatic QTc^b intervals. In patients with both abnormal automatic QTc^b and approximated QTc^f , a manual determination of QTc^f is necessary to identify actual QT interval prolongation.

In conclusion, automatic Bazett QTc calculation unreliably identifies patients with prolonged QTc interval. The proposed three-step strategy permits one to limit misinterpretation linked either to the use of Bazett or to automatic measurement.

The authors thank Frédéric Lirussi, Pharm.D. (Resident in Pharmacology, Division of Clinical Pharmacology, Paris, France), for remeasurement of electrocardiographic recording.

We propose an approximation of the Fridericia correction formula by use of a simple calculation that can be performed by clinicians without a scientific calculator, i.e. , without calculating the cubic root of the R-R interval in the Fridericia formula. The Fridericia formula (QTC^f = QT/

) can be simply decomposed into two parts: QT, the uncorrected QT interval in ms, and 1/

, the parameter of correction of this equation. Because R-R = 60/heart rate , the parameter 1/

is equal to 1/

First, it was calculated for heart rates ranging from 40 to 130 beats/min by increments of 1 beat/min. Second, this parameter was represented in the figure 4. Graphically, we observed that this parameter increases by approximately 5% for each increase of heart rate of 10 beats/min. The proposed approximation is shown in table 1. Approximated QTc is calculated by multiplying the uncorrected QT and the parameter of correction related to the measured heart rate. Finally, the approximated parameter was compared to Fridericia, resulting in a slight mean overestimation of 1.1 ± 2.0% (P < 0.0001).

Given an uncorrected QT of 380 ms and a heart rate of 93 beats/min, 5% of 380 is first calculated (mentally by dividing by 10, i.e. , suppressing the unity = 38, and then by dividing again by 2 = 38/2 = 19). For a heart rate of 93 beats/min, table 1indicates 115% of uncorrected QT; thus the result is QTc = QT + 10% of QT + 5% of QT; QTc = 380 + 38 + 19 = 437 ms. For this example, the QTc^f calculated from automatically measured raw QT and R-R intervals was 439 ms, and QTc^b reported by the device was 473 ms.