Response of QT interval in methadone maintenance treated patients to the rapid changes in heart rate provoked by brisk standing: Comparison to healthy controls and patients with long QT syndrome ☆ Orit Kliuk Ben Bassat, MD, a Einat Peles, PhD, d Shaul Schreiber, MD, b,d Miriam Adelson, MD, d David Zeltser, MD, a Sami Viskin, MD, c Arnon Adler, MD c, ⁎ a Department of Internal Medicine D, Tel-Aviv Sourasky Medical Center and Sackler-School of Medicine, Tel Aviv University, Tel Aviv, Israel b Department of Psychiatry, Tel-Aviv Sourasky Medical Center and Sackler-School of Medicine, Tel Aviv University, Tel Aviv, Israel c Department of Cardiology, Tel-Aviv Sourasky Medical Center and Sackler-School of Medicine, Tel Aviv University, Tel Aviv, Israel d Dr. Miriam & Sheldon G. Adelson Clinic for Drug Abuse Treatment and Research, Tel-Aviv Sourasky Medical Center and Sackler-School of Medicine, Tel Aviv University, Tel Aviv, Israel Abstract Background: Patients on methadone maintenance therapy are somehow similar to patients with congenital long QT syndrome (LQTS) because they have malfunction of potassium channels caused by a drug that cannot be easily discontinued. We tested patients on methadone therapy with the “stand-up” test, which has been shown to unravel pathologic QT-prolongation in congenital long-QT patients. Methods: “Stand-up” test results of methadone-users, healthy volunteers and congenital LQTS patients were compared. Methadone serum levels and doses were collected. The prognostic value of the test was evaluated after 4 years of follow-up. Results: The QT-response of methadone-users to the “stand-up” test resembled that of healthy volunteers more than the response of LQTS-patients. Differences in the QTc of methadone treated patients and controls, which were statistically significant at baseline, became no longer significant after standing. Within 52 months of follow-up, one patient had suffered unexplained death and one had documented ventricular tachycardia. Conclusions: The QT-response of methadone-users to the “stand-up” test is similar to that of healthy volunteers, not to that of LQTS-patients. © 2013 Elsevier Inc. All rights reserved. Keywords: Long QT syndrome; Methadone Introduction Patients treated with methadone for opiate-addiction represent a unique patient population from the cardiologists’ perspective. After all, methadone is an I Kr channel blocker that may provoke drug-induced acquired long QT syndrome (LQTS) and torsade de pointes. 1 Yet, as opposed to other forms of drug-induced LQTS that are treated by discontinu- ing the culprit, methadone cannot be stopped without risking serious opiate-withdrawal symptoms or returning to heroin use. Also, alternative drug treatment of opiate addiction is expensive and not readily available in most addiction- clinics. 2 Thus, patients treated with methadone are more alike patients with congenital long QT syndrome of the LQT2-type because they have truly long-lasting malfunction of the I Kr channel. In all forms of congenital and acquired LQTS, the risk for torsade de pointes roughly correlates with the degree of QT prolongation. 3 However, the correlation between the methadone dosage (or the methadone drug levels) and the degree of QT prolongation or the risk for torsade de pointes is not straightforward. In fact, different studies show inconsistent results with respect to the linear correlation between methadone dose and QTc. 4–11 We recently showed that the sudden tachycardia pro- voked by standing unravels pathologic QT prolongation in patients with congenital LQTS. Moreover, we showed that Available online at www.sciencedirect.com ScienceDirect Journal of Electrocardiology 46 (2013) 519 – 523 www.jecgonline.com ☆ Conflict of interest: none. ⁎ Corresponding author. Department of Cardiology, Tel Aviv Medical Center, Weizman 6, Tel Aviv 64239, Israel. E-mail address: arnonadler@gmail.com 0022-0736/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jelectrocard.2013.08.011