title: Drug-induced torsades de pointes in an underserved urban population. Methadone: is there therapeutic equipoise?
abstract: BACKGROUND
  Although it has been well established that methadone use can result in prolonged QTc/torsades de pointes (TdP) and has been labeled as one of the main drugs that cause TdP, it is still prescribed indiscriminately, and several cases of methadone-associated TdP have been seen in our community.
  
  
  METHODS
  Our objective was to determine the associated factors for prolonged QTc and the development of torsades de pointes (TdP) in our underserved patient population. We found 12,550 ECGs with prolonged QTc between 2002 and 2013. Medical records were reviewed in order to identify precipitating factors for prolonged QTc and to detect incidence of TdP.
  
  
  RESULTS
  We identified 2735 patients with prolonged QTc who met the inclusion criteria. Of these, 89 (3%) experienced TdP. There was a greater prevalence of HIV infection in the TdP group (11.2 vs. 3.7%, p < 0.001). Furosemide, hydrochlorothiazide, selective serotonin reuptake inhibitors (SSRIs), amiodarone, ciprofloxacin, methadone, haloperidol, and azithromycin were the drugs most often associated with prolonged QTc (31, 8.2, 7.6, 7.1, 3.9, 3.4 and 3.3%, respectively). However, the agents most commonly associated with TdP were furosemide (39.3%), methadone (27%), SSRIs (19.1%), amiodarone (18%), and dofetilide (9%). The medications with statistical significance in the multivariate analysis for TdP development in descending order were as follows: ranolazine (odds ratios [OR] = 53.61, 95% confidence interval [CI] 5.4-524, p < 0.001), dofetilide (OR = 25, CI 6.47-103.16, p < 0.001), voriconazole (OR = 21.40, CI 3.24-124.25, p < 0.001), verapamil (OR = 10.98, CI 2.62-44.96, p < 0.001), sotalol (OR = 12.72, 1.95-82.81, p = 0.008), methadone (OR = 9.89, CI 4.05-24.15, p < 0.001), and SSRI (OR = 2.26, CI 1.10-5.96, p < 0.001). This multivariate analysis revealed that amiodarone and HIV infection were not implicated in TdP.
  
  
  CONCLUSIONS
  Methadone was by far the leading medication implicated in the development of TdP and an independent predictor in both univariate and multivariate analyses despite the fact that it was not the most common QT-prolonging medication in our population.
authors.affiliation: Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Silver Zone, 10467, Bronx, NY, USA.|Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Romero
authors.affiliation: Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Baldinger
authors.affiliation: Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Silver Zone, 10467, Bronx, NY, USA.
authors.forename: David
authors.initials: D
authors.lastname: Goodman-Meza
authors.affiliation: Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Silver Zone, 10467, Bronx, NY, USA.
authors.forename: Krysthel
authors.initials: K
authors.lastname: Engstrom
authors.affiliation: Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Silver Zone, 10467, Bronx, NY, USA.
authors.forename: Carolina R
authors.initials: CR
authors.lastname: Valencia
authors.affiliation: Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Silver Zone, 10467, Bronx, NY, USA.
authors.forename: Anjani
authors.initials: A
authors.lastname: Golive
authors.affiliation: Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Silver Zone, 10467, Bronx, NY, USA.
authors.forename: Francisco
authors.initials: F
authors.lastname: Medrano
authors.affiliation: Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Silver Zone, 10467, Bronx, NY, USA.
authors.forename: Sabarivinoth
authors.initials: S
authors.lastname: Rangasamy
authors.affiliation: Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Silver Zone, 10467, Bronx, NY, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Makkiya
authors.affiliation: Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Silver Zone, 10467, Bronx, NY, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Fisher
authors.affiliation: Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Silver Zone, 10467, Bronx, NY, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Gross
authors.affiliation: Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Silver Zone, 10467, Bronx, NY, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Krumerman
authors.affiliation: Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Silver Zone, 10467, Bronx, NY, USA.
authors.forename: Soo
authors.initials: S
authors.lastname: Kim
authors.affiliation: Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Silver Zone, 10467, Bronx, NY, USA.
authors.forename: Mario J
authors.initials: MJ
authors.lastname: Garcia
authors.affiliation: Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Silver Zone, 10467, Bronx, NY, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Biase
authors.affiliation: Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Silver Zone, 10467, Bronx, NY, USA. kferrick@montefiore.org.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Ferrick
mesh_terms: D017677:Age Distribution; D015984:Causality; D015897:Comorbidity; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology; D005260:Female; D006801:Humans; D015994:Incidence; D008133:Long QT Syndrome / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology*; D008297:Male; D008507:Medically Underserved Area; D008691:Methadone / Q000009:adverse effects*; D008875:Middle Aged; D009519:New York City / Q000453:epidemiology; D012307:Risk Factors; D017678:Sex Distribution; D016171:Torsades de Pointes / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology*; D014505:Urban Population / Q000706:statistics & numerical data*
chemical_list: D008691:Methadone
keywords: Methadone; Prolonged QT; Torsades de pointes