Download QT dispersion: time for an obituary?

European Heart Journal (2000) 21, 955–957
doi:10.1053/euhj.2000.2070, available online at http://www.idealibrary.com on
QT dispersion: time for an obituary?
See page 1023 for the article to which this Editorial
refers
During the past decade, studies of QT dispersion[1]
have become popular and numerous publications
have reported some physiological and/or clinical
value of QT dispersion measurement. Among others,
increased QT dispersion was observed to be associated with QT interval prolongation due to drugs with
known proarrhythmic properties and to be less
increased on drugs with a low incidence of proarrhythmia[2,3]; to predict mortality in general epidemiological studies[4,5]; and to identify patients who
are at greater risk after surviving acute myocardial
infarction[6]. Treatment-related decrease of QT dispersion was reported to mark therapeutic efficacy in
the idiopathic long QT syndrome[7]. More recently,
however, seriously conducted studies have been published challenging the clinical usefulness of QT dispersion assessment[8–10]. Indeed, for most published
positive results obtained with QT dispersion, a
counterpart can be found showing the exact opposite.
Thus, the whole area of physiological and practical clinical utility of QT dispersion assessment is
controversial.
Moreover, despite different expressions of QT dispersion [11,12], the measurement suffers from a poor
reproducibility, both in terms of repeated measurement of the same electrocardiogram (ECG), irrespective of whether by the same or different observer, and
in terms of repeated ECGs in the same subject. This
might also be one of the reasons why, even in studies
reporting very strong statistical results, the normal
and abnormal values are substantially overlapping.
Despite the number of publications, no significant
improvement in the technology has really been made
since 1996 when Dr Surawicz concluded in his
review[13] that QT dispersion failed to pass four
mandatory tests for a clinical utility. The measurement methodology has still not been standardized,
the normal values have still not been well established,
the sensitivity and specificity of abnormal values
remain low, and the validity of the relevant
background hypotheses is still being discussed.
These controversies divided cardiac researchers
into strong believers and strong disbelievers of QT
dispersion. A number of scientific articles start from a
preamble that QT dispersion is an established technology of validated use while, at the same time,
serious publications denounce it as ‘the greatest
fallacy in electrocardiography in the 1990s’[14].
Perhaps the believers and disbelievers represent
two different poles of scientific and research attitude.
Some believe that the original concept of QT dispersion is correct merely because the technology can be
applied to existing ECGs, and that the results more or
less frequently (irrespective of the reproducibility)
statistically distinguish between clinically defined
groups. Others point to the flaws of QT dispersion
measurement and, based on the deep understanding
of the physics involved in the ECG lead theory, argue
that QT dispersion does not exist and that the published reports are based on misunderstanding and
unfounded speculations.
To resolve this controversy, one should perhaps
start by trying to answer the question of what is QT
dispersion.
What is QT dispersion and what is
not?
The group of the late Professor Campbell rekindled
the concept of QT dispersion at the end of the
1980s[1]. Following their original suggestion, there
has been speculation ever since that the increased
range of QT interval measurements is caused by a
regional heterogeneity of the duration of ventricular
repolarization. In more detail, it has been proposed
that different leads of the standard 12-lead ECG
project the repolarization signals of different myocardial regions differently and that, consequently,
increased dispersion is a measure of regional differences in the repolarization duration. Indeed, studies
comparing QT dispersion with the dispersion (that is,
the range) of the duration of monophasic action
potentials found a general correlation supporting this
hypothesis[15,16].
However, more recent studies have shown that a
similar value of QT dispersion is measured in full
12-lead ECGs and in their reconstruction from the
rectangular XYZ leads, in which the separate contribution by different myocardial regions has been
effectively filtered out[17]. It has also been shown that
QT dispersion values correlate with parameters of
vectorcardiographic T loop morphology[18]. Based on
these results, it has been proposed that the different
projections of the T wave vector into the different
ECG leads are essential and that an increase of QT
dispersion merely means an unusual projection of a
more complicated T wave loop.
2000 The European Society of Cardiology
956
Editorials
Most recently, an attempt has been made to
measure the ECG components independent of the
vectorcardiographic T loop, speculating that such
components more closely represent regional myocardial heterogeneity. While such non-dipolar components differ between different clinical different
groups, their correlation with QT dispersion is almost
non-existent[19].
After all, studies showing a correlation between the
dispersion of monophasic action potentials and the
QT dispersion measured in surface ECGs do not
actually prove that both these technologies address
precisely the same entity. If an increased heterogeneity exists in the durations of monophasic action
potentials, the repolarization sequence is clearly more
disturbed, the vectorcardiographic T wave loop is
more abnormal, the projections of the loop into the
standard ECG leads are more complicated, the
localization of the T wave offset in individual leads
is more difficult, and an increased QT dispersion is
measured.
The practical difficulty in localizing T wave offset
may actually also play an important role. More
abnormal T wave patterns are known to cause greater
difficulties in QT interval measurement. Hence, a
measurement bias cannot be excluded leading to
increased QT dispersion values in ECGs where the T
wave offset is less clearly defined. Since such cases are
more frequent in abnormal than normal ECGs, a
statistically significant difference may easily be contributed to, if not directly achieved by a bias in the
measurement error.
Based on the most recent studies, it seems safe to
conclude that the original concept of portraying QT
dispersion as a direct measure of the regional heterogeneity of myocardial refractoriness is seriously
flawed. At the same time, disproving this concept is
not a good reason for stating that ‘QT dispersion
does not exist’. While QT dispersion is not an expression of regional heterogeneity of myocardial refractoriness, the measurement of QT dispersion seems
to be an approximate expression of repolarization
abnormalities. Certainly, it is a very imprecise and
imperfect expression of such abnormalities and it
suffers from all the problems that were already
mentioned (reproducibility, stability, etc.). However,
it seems fair to say that we presently have no decent
and widely available alternative to address repolarization abnormalities in 12-lead ECGs.
What is the meaning of QT dispersion
studies?
If we accept the concept that increased QT dispersion
is a primitive quantifier of what is otherwise called
Eur Heart J, Vol. 21, issue 12, June 2000
‘unspecific T wave changes’, it is not unreasonable to
express the measurement numerically and to subject it
to statistical evaluation. True, we must not forget that
the measurement of QT dispersion is usually dependent on the operator and on the quality of the
analysed ECGs, that it is poorly reproducible and
that the electrophysiological background is only very
loosely defined. However, if we understand all this,
QT dispersion is better than the verbal description of
more or less expressed unspecific T wave changes.
In other words, even a primitive, imprecise and
imperfect approach is better than nothing.
Having this understanding in mind, we are in a
clear position to interpret experimental studies that
involve QT dispersion assessment. In this issue James
et al. present an elegant study showing that psychological stress increases QT dispersion in patients with
coronary artery disease but not in patients in whom
coronary artery disease has not been documented [20].
If we read ‘approximate measure of repolarization
abnormalities’ instead of ‘QT dispersion’, the study
makes a lot of sense. Coronary artery disease is likely
to make the ventricular myocardium more susceptible
to various provocations and it is fully plausible that
in patients with ischaemic disease, serious repolarization abnormalities can be induced by acute physiological stress. The authors of the study are right in
speculating that this might be the mechanism by
which psychological stress is proarrhythmic in some
cardiac patients. Their observation is another important piece for the mosaic of our apprehension of
the importance of repolarization abnormalities in
arrhythmogenesis.
The value of the message portrayed by James et al.
does not seem to be particularly reduced by the fact
that their study used a measurement technology the
electrophysiological basis of which is controversial
and the precision of which is almost non-existent.
True, if the study were repeated, it is highly unlikely
that the same numerical values would have been
observed and the same statistical significances
achieved. Nevertheless, that is a problem of the
presently available methodology for repolarization
assessment rather than a problem of the pathophysiological observation and of its clinical relevance.
Since QT dispersion is a very crude and very
imprecise method for the assessment of repolarization
abnormalities, it is plausible to speculate that minute
repolarization changes might be induced by acute
psychological stress even in non-ischaemic hearts
where the changes are too tiny to be detected by a
technology as imperfect as QT dispersion. Hence, it is
the difference in the response observed between
patients with and without ischaemic heart disease
which is the true message by James et al.
Editorials
What is the future of QT dispersion?
The slowly emerging understanding that QT dispersion is nothing more than a very crude way of
expressing repolarization abnormalities has clear implications for further advances of the field of study.
By relying on the localization of the end of the T wave
in individual ECG leads, QT dispersion is not only
imprecise, it also ignores the morphologies of the T
wave. The same value of QT dispersion may easily be
measured in ECGs in which the T wave patterns are
normal and in cases where the T wave is grossly
abnormal including inverted, notched and biphasic
morphologies.
Hence, other more precise and comprehensive
descriptors of abnormalities of myocardial repolarization are badly needed. QT dispersion should
certainly not be taken as a gold standard for a
non-invasive estimate of repolarization abnormalities
suitable for judging new concepts of repolarization
assessment. On the contrary, once a more focused
technology for repolarization assessment is developed
and once it is made widely available to the research
community, the prospect of QT dispersion as a technology seems to be bleak. At the same time, since
we are probably only at the beginning of detailed
repolarization studies enabled by high quality digital
ECGs, QT dispersion seems to be a small step in the
correct direction.
Despite the serious difficulties with the concept of
QT dispersion and despite the fact that a clear
publication bias exists towards positive findings, the
huge number of studies showing some meaningful
results with QT dispersion measurements cannot be
dismissed lightly. Repolarization is important!
M. MALIK
Department of Cardiological Sciences,
St. George’s Hospital Medical School,
London, U.K.
References
[1] Day CP, McComb JM, Campbell RW. QT dispersion: an
indication of arrhythmic risk in patients with long QT
intervals. Br Heart J 1990; 63: 342–4.
[2] van de Loo A, Klingenheben T, Hohnloser SH. Amiodarontherapie nach Sotalol-induzierter Torsade de pointes: QTVerlangerung und QT Dispersion zur Differenzirung
proarrhythmischer Effekte. Zeitschrift für Kardiologie 1994;
83: 887–90.
957
[3] Hohnloser SH, Singh BN. Proarrhythmia with class III antiarrhythmic drugs: definition, electrophysiologic mechanisms,
incidence, predisposing factors, and clinical implications. J
Cardiovasc Electrophysiol 1995; 6: 920–36.
[4] de Bruyne MC, Hoes AW, Kors JA, Hofman A, van Bemmel
JH, Grobbee DE. QTc dispersion predicts cardiac mortality in
the elderly: the Rotterdam study. Circulation 1998; 97: 467–
72.
[5] Elming H, Holm E, Jun L et al. The prognostic value of the
QT interval and QT interval dispersion in all-cause and
cardiac mortality and morbidity in a population of Danish
citizens. Eur Heart J 1998; 19: 1391–400.
[6] Glancy JM, Garratt CJ, Woods KL, de Bono DP. QT
dispersion and mortality after myocardial infarction. Lancet
1995; 345: 945–8.
[7] Priori SG, Napolitano C, Diehl L, Schwartz PJ. Dispersion of
QT interval. A marker of therapeutic efficacy in the idiopathic
long QT syndrome. Circulation 1994; 89: 1681–9.
[8] Kautzner J, Malik M. QT Dispersion and its Clinical Utility.
PACE 1997; 20: 2625–40.
[9] Zabel M, Klingenheben T, Franz MR, Hohnloser SH. Assessment of QT dispersion for prediction of mortality of arrhythmic events after myocardial infarction: results of a
prospective, long-term follow-up study. Circulation 1998; 97:
2543–50.
[10] Gang Y, Elliott P, McKenna WJ et al. QT dispersion and risk
factors for sudden cardiac death in patients with hypertrophic
cardiomyopathy. Am J Cardiol 1998; 82: 1514–19.
[11] Hnatkova K, Malik M, Kautzner J, Gang Y, Camm AJ.
Adjustment of QT dispersion assessed from 12 lead electrocardiograms for different numbers of analysed electrocardiographic leads: comparison of stability of different
methods. Br Heart J 1994; 72: 390–6.
[12] Langley P, Di Bernardo D, Murray A. Comparison of three
measures of QT dispersion. Computers in Cardiology 1999: in
press.
[13] Surawicz B. Will QT dispersion play a role in clinical decisionmaking? J Cardiovasc Electrophysiol 1996; 7: 777–84.
[14] Rautaharju PM. QT and Dispersion of ventricular repolarization: The greatest fallacy in electrocardiography in the 1990s.
Circulation 1999; 18: 2477–8.
[15] Zabel M, Portnoy S, Franz MR. Electrocardiographic indexes
of dispersion of ventricular repolarization: an isolated heart
validation study. J Am Coll Cardiol 1995; 25: 746–52.
[16] Zabel M, Lichtlen PR, Haverich A, Franz MR. Comparison
of ECG variables of dispersion of ventricular repolarization
with direct myocardial repolarization measurements in human
heart. J Cardiovasc Electrophys 1998; 9: 1279–84.
[17] Lee KW, Kligfield P, Okin PM, Dower GE. Determinants of
precordial QT dispersion in normal subjects. J Electrocardiol
1998; 31 (Suppl): 128–33.
[18] Kors JA, van Herpen G, Van Bemmel JH. QT dispersion as
an attribute of T-loop morphology. Circulation 1999; 99:
1458–63.
[19] Malik M, Acar B, Yap Y-G, Yi G. QT dispersion does not
express spatial heterogeneity of ventricular refractoriness in 12
lead ECGs (Abstr). Circulation 1999; 100 (Suppl): I-245.
[20] James PR, Taggart P, McNally ST, Newman SP, Sporton SC,
Hardman SMC. Acute psychological stress and the propensity
to ventricular arrhythmias: evidence for a linking mechanism.
Eur Heart J 2000; 21: 1023–8.
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