QT Analysis: Problems and Prospects

Paul Kligfield

Division of Cardiology, Weill Medical College of Cornell University, and the
Cornell Campus of The New York- Presbyterian Hospital, New York, New York, USA

Correspondence: P Kligfield, Division of Cardiology, Cornell Medical Center, 525 East 68^th Street, New York, NY 10021 USA.
E-mail: pkligfi@med.cornell.edu, phone 212-746-4686, fax 212-746-8561

Introduction

As a consequence of the interval-duration relationship, the QT interval of the ECG varies directly with cycle length. For much of the twentieth century, the QT interval has been measured from a single ECG lead and corrected for rate by exponential cycle-length equations derived from small numbers of subjects. It has become well recognized that abnormalities of the QT interval can result from congenital disorders, electrolyte abnormalities, drug effects, hypoxia and ischemia, and a variety of autonomic nervous system affections. Clinical recognition of the arrhythmogenic potential of congenital and acquired forms of the long QT interval, particularly as a result of direct or indirect effects of drugs on myocardial ionic channel function, has refocused attention on the definition, measurement, and recognition of QT interval abnormality.

Definition and Measurement of the QT Interval

A large number of methodologic problems affect QT interval determination. There is no consensus regarding which lead or set of leads should routinely be used to measure the QT interval, even though recent attention to the presence of QT dispersion on the surface ECG highlights the importance of this factor on test outcome. Varying definitions of the end of the T wave include estimation of its apparent baseline termination, the nadir of T-U fusion, and extrapolation to baseline from its steepest descending point, each of which produces different results. In addition, variable inclusion or exclusion of prominent U waves leads to markedly differing measurements. Alternative determinants of the end of the T wave can be derived from simultaneous lead recordings, since the earliest onset of QRS and the latest offset of T can be defined from spatial vector magnitude transformations or other combinations of leads; these will produce different measurements than those obtained from single leads. Based on linear regression data from resting ECGs in large numbers of normal men in Framingham, the tendency of the widely used Bazett correction to overestimate QT at shorter cycle lengths and of the Fredericia correction to less importantly underestimate QT at corresponding shorter cycle lengths becomes apparent. It is clear that QT interval ranges differ between men and women, but differences due to race and to age require further clarification. Even the recognition of QT change within an individual can vary according to whether abnormality is defined by absolute rate-corrected duration or, alternatively, by an absolute increment in duration. QT subintervals, such as QTpeak and Tpeak-Tend or JT intervals provide alternative measurements that also are subject to these methodologic problems. Limitations are further confounded by the precision and reproducibility of the measurement itself, which in turn is influenced by the experience of the reviewer, standardization of procedure, and use of computer assistance. Ultimately, the QT interval is a simple temporal measurement of resting ECG repolarization. Alternative evaluation of ECG repolarization is available with principle component analysis, which examines subtleties of T wave morphology by comparison of eigenvectors and may provide insights and information not contained in the QT interval itself.

Dynamic Behavior of the QT Interval

The QT interval of an individual depends on physiologic factors beyond simple cross-sectional measurement of cycle length alone. Evaluation of the QT interval from a single ECG fails to consider rate-dependent restitution and other rate-independent components of QT behavior that can be detected from longitudinal examination of the changing QT interval. Of course, methodologic problems affecting QT measurement on the standard ECG also affect the accuracy and reproducibility of serial measurements within an individual. The relation of QT interval to both rate-dependent and rate-independent factors can be examined during the relatively brief time window of a graded exercise protocol or throughout a longer term period that includes a wide range of activities of daily living. Accordingly, both exercise and ambulatory electrocardiography can acquire information regarding QT-cycle length changes with time that provide insight into the dynamic behavior of the QT interval and its underlying neurohumoral determinants. Examined in this way, the QT- heart rate or QT- cycle length relationship can be seen to be more dynamic during the day than at night, even when adjusted for differences in underlying heart rate, and even more dynamic during the sympathetic stimulation associated with short term exercise. The slopes of these relationships can be defined within individuals to provide insight into autonomic balance and can vary with sex, age, and a variety of myocardial processes that affect the heart. Data within an individual can be extrapolated to a constant cycle length for assessment and comparison within groups. QT/cycle length slopes have been shown to be highly variable between subjects but stable within individuals, both during exercise and during longer term recording. From these analyses, QT modulation by rate has been shown to be greater in women than in men. Circadian modulation of QT by cycle length appears to decrease with age. These findings can offer alternative and additional insight into the effects of disease and pharmacological intervention on the ECG by providing new, dynamic definitions of normal and abnormal repolarization. Both standard and dynamic aspects of QT analysis will be explored by the contributors to this session.

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