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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Heart Rhythm. Author manuscript; available in PMC Oct 1, 2012.
Published in final edited form as:
PMCID: PMC3154568
NIHMSID: NIHMS283184

Factors Affecting the Degree of QT Prolongation with Drug Challenge in a Large Cohort of Normal Volunteers

QT Prolongation with Drug Challenge in Normals
Prince J. Kannankeril, MD, MSCI,* Kris J. Norris, RN, Shannon Carter, RN, and Dan M. Roden, MD, FHRS

Abstract

Background

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

Objective

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 18-40 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<0.001) and QTc from 406 ± 15 ms to 446 ± 33 ms (P<0.001). The ΔQTc did not correlate with baseline QTc (Pearson correlation 0.016, P = 0.8). Post-drug QTc was correlated weakly with pre-drug QTc (Pearson correlation 0.484, p<0.001), and strongly with ΔQTc (Pearson correlation 0.882, P < 0.001). ΔQTc was identical for men and women (39 ± 29 ms vs. 39 ± 27 ms, P = 0.9), but displayed significant differences among body mass index categories (P<0.001). 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.

Conclusions

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.

Keywords: Electrocardiography, Obesity, Ion channels, Pharmacology, QT interval

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