Analysis
Shortened QT interval: a distinctive feature of the dysautonomia of chronic fatigue syndrome

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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 ± 0.02 seconds and QTc on tilt, 0.385 ± 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.

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, 2, 3, 4, 5, 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 parasympathetic 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, 8, 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 are poorly understood despite claims that CFS might be caused by viral, immune, or psychogenic insults.11, 12 Previous studies have documented a close connection between impairment of autonomic functions and CFS.13, 14, 15, 16, 17, 18 In patients with CFS, central nervous system abnormalities on magnetic resonance imaging19 and single photon emission tomography20 have been described. In addition, disruption of the hypothalamic-pituitary-adrenal axis and serotoninergic and noradrenergic pathways21 and a “distal dysautonomia” have been demonstrated in CFS.22

Because autonomic nervous functioning is frequently abnormal in CFS, we examined whether the corrected QT interval (QTc) in CFS differs from QTc in other populations. On a Medline search, no previous publications on QT interval in patients with CFS were found.

Section snippets

Patients and methods

The patients were referred to our clinic for appraisal of occult dysautonomia or for evaluation of unexplained syncope. All participants gave informed consent and our institution's committee for human research approved the study. The patients were not taking medications for at least 2 weeks before the study. Recordings of patients previously studied23, 24, 25 were reevaluated to measure QTc intervals in the CFS group, in comparison with control groups. Control groups were selected such as to

Phase I study

Coefficients of variation of the QT measurements by the same observer were 2.18% and 1.9%, respectively. On comparison of measurements by different observers, the coefficients of variation of the QT measurements were 2.25% and 2.19%, respectively.

Uncorrected ECG measurements in supine and tilt phases of the HUTT are shown in Table 1. Except in healthy subjects, the supine R-R intervals were longer and QT intervals shorter than corresponding measurements on tilt (P = .01 to <.0001). The QTc

Discussion

A relatively short QTc interval was found in patients with CFS, significantly different from control patients. Usually, QTc in the range of 0.400 to 0.440 seconds is considered to be normal.35 Although the upper limit of normal for the QTc is well defined and its prolongation has been used as an ECG marker to identify patients at risk for sudden arrhythmogenic death, there is no consensus on the lower limit of normal for the QTc or its clinical significance. Persistently short QTc is most often

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