Torsades de pointes (TdP) is a polymorphic ventricular tachycardia associated with
prolongation of the heart rate-corrected QT (QTc) interval on the electrocardiogram (ECG).
TdP can result in catastrophic outcomes, including sudden cardiac death. QTc interval
prolongation is a well-known adverse event associated with methadone use. While some risk
factors for methadone-associated QTc interval prolongation and TdP have been identified, the
contribution of interacting drugs and concomitant administration of other QTc
interval-prolonging agents to overall risk has not been determined. The effect of ECG
screening and monitoring on clinical outcomes in patients taking methadone has not been
evaluated, and clinical opinion regarding routine ECG and risk factor monitoring varies.
Twelve lead ECGs are costly and time-intensive for clinic staff. ECG screening in selected
patients based on presence of QTc interval risk factors, rather than broadly in all patients
taking methadone, would facilitate more targeted, strategic QTc interval monitoring. The
FDA-approved AliveCor® handheld smart phone/tablet device records a single lead ECG (iECG)
within 30 seconds. Use of this device may facilitate simpler, more rapid and less costly ECG
monitoring in patients receiving care in narcotic treatment centers.
Our long-term goals are to determine mechanisms by which drugs cause arrhythmias, to identify
patients at greatest risk of drug-induced arrhythmias, and to determine safe and effective
methods for prevention and management of drug-induced arrhythmias.
Specific Aim 1: Identify independent risk factors for methadone-induced QTc interval
prolongation in patients undergoing care in a narcotic treatment center.
Research Design: This will be a retrospective/prospective analysis of ECGs and health
information from patients receiving methadone therapy in the Eskenazi Health Midtown Narcotic
Treatment Center in Indianapolis, IN. Currently, at the Midtown Narcotic Treatment Center,
baseline 12-lead ECGs are recorded for all patients prior to initiation of methadone therapy;
follow-up ECGs are obtained approximately 2 weeks after methadone initiation only in patients
with a baseline prolonged QTc interval. At the start of the study, methadone-treated patients
who have not had follow-up ECGs on methadone therapy will be identified and contacted
prospectively. Those consenting to participation will undergo a follow-up 12-lead ECG to
determine QTc interval during methadone maintenance therapy. For all patients, retrospective
analysis of the electronic medical record will be performed to document sex, pregnancy
status, age, family history, current and past medical history, and concomitant use of
prescribed, over the counter, and illicit drug use with the aim to identify all potential
risks. QTc interval prolongation will be defined as QTc interval ≥ 500 ms or an increase in
QTc interval of ≥ 60 ms compared with the baseline QTc interval. Electronic health
information variables will be compared in patients who develop methadone-associated QTc
interval prolongation versus those who do not using univariate analysis. Patients with
prolonged QTc interval at baseline will be excluded from the study.
Specific Aim 2: Validate the handheld AliveCor® smart phone/tablet iECG device as a simple,
rapid method of monitoring QTc intervals in methadone-treated patients in a narcotic
Research Design: A separate cohort of patients will be utilized to validate the AliveCor®
device for use in measuring QTc intervals in patients initiated and maintained on methadone
in a narcotic treatment center. Twelve lead ECGs and simultaneous single lead ECGs using the
AliveCor® device will be recorded for all newly enrolled patients at baseline and again after
six weeks of methadone therapy. The QTc identified by the 12-lead ECG will be compared to the
single lead ECG for all baseline and follow-up recordings to validate the use of the
AliveCor® device for potential use in narcotic treatment centers to reduce cost and save
time. Comparison of QTc intervals between the 12-lead and single lead measurements will be
performed using the Bland-Altman method for analysis of measurement agreement. The mean and
95% confidence interval of the difference in QTc interval between the two methods will be
This will be a pilot study to justify a larger extramural study to develop and validate a
risk score for methadone-induced QTc interval prolongation and to use the handheld ECG device
for QTc interval monitoring in patients identified as high-risk using this risk score. Our
rationale is that identification of risk factors for methadone-induced QTc interval
prolongation and quantification of degree of risk conferred by each risk factor will
ultimately reduce the incidence and risk of QTc interval prolongation through targeted ECG
monitoring of patients at highest risk and modulation of modifiable risk factors.