James, Paula Rachael; (2003) Insights into the arrhythmogenic substrate of the human heart: An evaluation of dynamic influences on QT dispersion. Doctoral thesis (M.D), UCL (University College London).

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Abstract

Strong experimental evidence implicates enhanced dispersion of repolarisation with arrhythmogenesis. The inability to assess directly these parameters in man, coupled with the more complex electrophysiological changes of diseased human hearts compared with experimental models, has hampered the search for underlying mechanisms. However, there was great interest following the report that a measure of dispersion of repolarisation could be gained from the twelve lead electrocardiogram, by measuring QT dispersion. Much of the work in this area has centred on the measurement of QT dispersion from resting 12 lead electrocardiograms and it has often proved a disappointing tool for predicting those at increased risk of arrhythmic/sudden cardiac death. Yet even patients at increased risk only develop arrhythmias periodically, as a result of an alteration in the electrophysiological substrate, and thus at times dispersion of repolarisation may be normal. There has been almost an acceptance that QT dispersion is influenced by heart rate and most investigators have employed some form of rate correction despite a lack of evidence that this is appropriate. The effect on QT dispersion of heart rate change was examined during both steady state and single interval changes. A likely trigger for acute changes in dispersion of repolarisation is acute mental stress in vulnerable individuals. Psychological stress is recognised to be a factor in sudden death. A series of patients, with and without coronary artery disease, are presented in whom the influence of acute psychological stress, induced by psychometric testing, was examined. Another group of individuals at risk from arrhythmias are those with abnormal ventricular function. Strong experimental evidence supports the influence of mechano-electric feedback, whereby mechanical perturbations alter the electrophysiological substrate of the heart. The effect of an abrupt change in ventricular load on QT dispersion, within the physiological range, in patients with and without abnormal ventricular function forms the final component of this thesis. In total one hundred patients were studied, all prospectively.

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