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Twenty-Four–Hour Measures of Heart Rate–Corrected QT Interval, Peak-to-End of the T-Wave, and Peak-to-End of the T-Wave/Corrected QT Interval Ratio During Antipsychotic Treatment

Tümüklü, Mevhibe N., MD*; Tümüklü, Mustafa M., MD*†; Nesterenko, Vladislav, PhD; Jayathilake, Karu, MA; Beasley, Charles M. Jr, MD; Meltzer, Herbert Y., MD

Journal of Clinical Psychopharmacology: March/April 2019 - Volume 39 - Issue 2 - p 100–107
doi: 10.1097/JCP.0000000000001003
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Purpose/Background Prolonged ventricular repolarization, measured by heart rate–corrected QT interval (QTc) prolongation, might be a biomarker for risk of torsade de pointes (TdP) and sudden cardiac death. However, the predictive value of QTc has been challenged, and a component of QTc, peak-to-end of the T-wave (Tpe), and a high Tpe/QT ratio might be superior biomarkers because they better reflect increased transmural dispersion of ventricular myocyte repolarization, which can lead to TDP. The purpose of this pilot study was to provide the first measurements of heart rate, QTc, Tpe, Tpe/QTc, and their variability over 24 hours in medication-free patients with schizophrenia, during treatment with ziprasidone or other antipsychotic drugs, and healthy controls.

Methods Subjects included 12 patients treated with ziprasidone, 30 treated with other antipsychotic drugs, 3 unmedicated patients, and 15 normal controls. Subjects underwent 24-hour analog Holter recording, and the recordings were digitized. A cardiologist blind to treatment selected multiple 10-cycle segments throughout each recording and measured the electrocardiogram metrics.

Results Variability in QTc, Tpe, and Tpe/QTc over the 24 hours was present in all groups; 91.1% of patients and 100% of controls had 1 or more QTc values of 450 milliseconds or greater. Mean QTc length was significantly greater in the ziprasidone-treated than the non–ziprasidone-treated patients (P = 0.02). Mean Tpe was not elevated in the ziprasidone patients, whereas mean Tpe/QTc was lower (P < 0.01).

Conclusions The large variability in QTc, Tpe, and Tpe/QTc observed supports the need for 24-hour electrocardiogram recordings to provide an accurate assessment of risk of TdP. Heart rate–corrected QT interval alone does not capture the risk of TdP.

From the *Vanderbilt School of Medicine, Nashville, TN;

Kent Hospital, Izmir, Turkey;

Masonic Medical Research Laboratory, Utica, NY;

§Department of Psychiatry, Northwestern University Feinberg School of Medicine, Chicago, IL; and

Beasley Pharmaceutical and Biotechnology Consulting, LLC, Indianapolis, IN.

Received June 6, 2010; accepted after revision December 5, 2018.

M.N.T. is in private practice in Izmir, Turkey.

Reprints: Herbert Y. Meltzer, MD, Department of Psychiatry, Northwestern University Feinberg School of Medicine, Ward Bldg Room 12-104, 303 E Chicago Ave, Chicago, IL 60611 (e-mail: h-meltzer@northwestern.edu).

M.N.T. was supported by a fellowship from Gaziosmanpasa University. Rozinn Electronics Inc (Glendale, NY) donated the software. Donations from the Weissman Foundation and a grant from Eli Lilly supported a portion of the data collection and data analysis.

Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.psychopharmacology.com).

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