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. 2011 Oct;8(10):1530-4.
doi: 10.1016/j.hrthm.2011.03.042. Epub 2011 Mar 21.

Factors affecting the degree of QT prolongation with drug challenge in a large cohort of normal volunteers

Prince J Kannankeril  1 , Kris J Norris, Shannon Carter, Dan M Roden
Affiliations

Factors affecting the degree of QT prolongation with drug challenge in a large cohort of normal volunteers

Prince J Kannankeril et al. Heart Rhythm. 2011 Oct.

Abstract

Background: The degree of QT prolongation by drug is highly variable and related to risk for polymorphic ventricular tachycardia due to drugs.

Objective: The purpose of this study was to determine factors that affect the degree of QT prolongation by drugs.

Methods: QT and QTc were measured before and after administration of the QT-prolonging drug ibutilide in 253 normal volunteers aged 18 to 40 years. Drug effect on QTc prolongation was defined as ΔQTc = QTc after drug minus QTc before drug.

Results: Ibutilide prolonged QT from 396 ± 31 ms to 418 ± 39 ms (P <.001) and QTc from 406 ± 15 ms to 446 ± 33 ms (P <.001). ΔQTc did not correlate with baseline QTc (Pearson correlation 0.016, P = .8). Postdrug QTc was correlated weakly with predrug QTc (Pearson correlation 0.484, P <.001), and strongly with ΔQTc (Pearson correlation 0.882, P <.001). ΔQTc was identical for men and women (39 ± 29 ms vs 39 ± 27 ms, P = .9) but displayed significant differences among body mass index categories (P <.001). Overweight (48 ± 27 ms) and obese (61 ± 31 ms) subjects had significantly more QT prolongation by drug than normal (31 ± 25 ms) or underweight (24 ± 12 ms) subjects.

Conclusion: QT prolongation by ibutilide does not correlate to baseline QTc and does not differ between men and women. Overweight and obese subjects have greater drug effect on QTc than subjects with normal or low body mass index. These findings have implications for drug-induced long QT syndrome.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1. Scatterplots of baseline QTc, post-drug QTc, and ΔQTc
The ΔQTc shows no correlation to baseline QTc (P=0.8, top left panel). The post-drug QTc correlates significantly, but weakly, with baseline QTc (P<0.001, R2=.23, right panel), and strongly with ΔQTc (P<0.001, R2=.77, bottom left panel).
Figure 2
Figure 2. Body Mass Index affects ΔQTc
The ΔQTc (mean + 1 SEM) is plotted for all subjects by BMI category. There is no significant difference in ΔQTc between underweight and normal subjects, but overweight and obese subjects have significantly more QT prolongation by drug.
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