Correction of the QRS duration for heart rate

To determine the clinical value of correcting the QRS duration for heart rate.

We recently observed [1] that the QRS duration shortens during spontaneous increases in heart rate. In the current study, we analyzed ECG and pharmacokinetic data of 21 subjects who received quinidine in a recent study [2]. They experienced the expected post-quinidine increase in heart rate, allowing us to determine if quinidine's well-known QRS prolongation might be attenuated due to the concomitant rate increase.

In a crossover-designed study, after baseline ECG recording, the subjects received quinidine 400 mg orally or placebo, and ECGs and quinidine plasma concentrations were then obtained at 15 prespecified timepoints over 24 h. The previously determined QRS-RR regression slope (0.0125) [1] was used to rate-correct QRS. Change in QRS from baseline (dQRS) and rate-corrected change in QRS from baseline (dQRSc) over time were plotted with the mean quinidine concentration and the correlation of plasma concentration with dQRS and dQRSc was assessed by pairwise correlation and linear regression.

There was a statistically significantly greater increase in heart rate at all timepoints combined in the quinidine arm compared with the placebo arm (9.9 ± 6.80 vs. 5.2 ± 7.42, respectively, p < 0.0001). dQRSc was significantly greater at all timepoints combined compared with dQRS (1.99 ± 4.824 vs -0.68 ± 4.640 msec, respectively, p < 0.0001). dQRS correlated poorly with quinidine plasma concentration (p = 0.127), with no clear change in QRS observed. On the other hand, dQRSc correlated well with quinidine concentration (p = 0.010), with a clear rise and fall in dQRSc that mirrored the rise and fall of quinidine concentration.

Rate correction of the QRS duration improves detection of QRS prolongation in the presence of heart rate change.

Using the mean QRS - RR slope determined previously in normal volunteers [1], we corrected the QRS duration for its known dependency on heart rate in 21 subjects who received quinidine and experienced the expected post-quinidine increase in heart rate in a recent clinical trial [2]. We found that uncorrected QRS did not correlate with quinidine concentration (p = 0.127), while rate-corrected QRS correlated well (p = 0.010) and mirrored the rise and fall of quinidine concentration. Rate correction of the QRS duration improves detection of QRS prolongation in the presence of heart rate change.