ARTICLE IN PRESS Shortened QT interval: a distinctive feature of the dysautonomia of chronic fatigue syndrome Jochanan Naschitz, MD a, 4 , Madeline Fields, MD a , Hillel Isseroff, MD a , Dauod Sharif, MD b , Edmond Sabo, MD a , Itzhak Rosner, MD c a Department of Internal Medicine A, Bnai Zion Medical Center and dRappaport FamilyT Faculty of Medicine, Technion-Israel Institute of Technology, P.O. Box 4940, Haifa 31048, Israel b Heart Institute, Bnai Zion Medical Center and dRappaport FamilyT Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31048, Israel c Department of Rheumatology, Bnai Zion Medical Center and dRappaport FamilyT Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31048, Israel Received 9 September 2005 Abstract Purpose: Because autonomic nervous functioning is frequently abnormal in chronic fatigue syndrome (CFS), we examined whether the corrected QT interval (QTc) in CFS differs from QTc in other populations. Methods: The QTc was calculated at the end of 10 minutes of recumbence and the end of 10 minutes of head-up tilt. In a pilot study, groups of 15 subjects, CFS, and controls, matched for age and sex, were investigated. In a second phase of the study, the QTc was measured in larger groups of CFS (n = 30) and control patients (n = 96) not matched for demographic features. Results: In the pilot study, the average supine QTc in CFS was 0.371 F 0.02 seconds and QTc on tilt, 0.385 F 0.02 seconds, significantly shorter than in controls ( P = .0002 and .0003, respectively). Results of phase II confirmed this data. Conclusions: Relative short QTc intervals are features of the CFS-related dysautonomia. The significance of this finding is discussed. D 2006 Published by Elsevier Inc. Keywords: Corrected QT interval; Electrocardiography; Chronic fatigue syndrome; Dysautonomia 1. Introduction The QT interval on the surface electrocardiogram (ECG) reflects depolarization and repolarization of myocardial cells. A variety of factors may influence the QT interval, including heart rate (HR), genetic abnormalities of the potassium channel, electrolyte disturbances, myocardial ischemia, drugs, and sympathetic and parasympathetic tone [1- 6]. Changes in autonomic tone may condition the QT interval directly by altering repolarization kinetics of myocardial cells through influences on ion currents or indirectly by modulating the HR [7]. The effects of the autonomic nervous system on the QT interval have been studied in patients with combined sympathetic and para- sympathetic failure, such as patients with idiopathic pure autonomic failure, familial dysautonomia, multiple system atrophy, and Parkinson’s disease, as well as patients with diabetic autonomic neuropathy and chronic liver disease [7-9]. The above conditions often are associated with abnormally prolonged QT intervals. In contrast, patients with isolated sympathetic failure, such as subjects with congenital deficiency of dopamine-beta-hydroxylase, have a normal duration of the QT interval [7]. A dysautonomia that differs from classic autonomic failure has been recognized in patients with the chronic fatigue syndrome (CFS). Chronic fatigue syndrome is defined as cinically evaluated, medically unexplained fatigue of at least 6 months’ duration that is of new onset, is not a result of ongoing exertion, not substantially alleviated by rest, and substantially reducing previous levels of activity [10,11]. The etiology and pathogenesis of CFS 0022-0736/$ – see front matter D 2006 Published by Elsevier Inc. doi:10.1016/j.jelectrocard.2005.10.014 4 Corresponding author. E-mail address: naschitz@tx.technion.ac.il (J. Naschitz). Journal of Electrocardiology xx (2006) xxx – xxx www.elsevier.com/locate/jelectrocard