title: Factors affecting the degree of QT prolongation with drug challenge in a large cohort of normal volunteers.
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.
  
  
  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.
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. prince.kannankeril@vanderbilt.edu
authors.forename: Prince J
authors.initials: PJ
authors.lastname: Kannankeril
authors.forename: Kris J
authors.initials: KJ
authors.lastname: Norris
authors.forename: Shannon
authors.initials: S
authors.lastname: Carter
authors.forename: Dan M
authors.initials: DM
authors.lastname: Roden
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D016009:Chi-Square Distribution; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology*; D008297:Male; D013449:Sulfonamides / Q000009:adverse effects*
chemical_list: D000889:Anti-Arrhythmia Agents; D013449:Sulfonamides; C067192:ibutilide