From the Hôpital Lariboisière, Paris, France.
Correspondence to Philippe Coumel, MD, FESC, Hôpital Lariboisière, 2, rue Ambroise-Paré, 75015 Paris, France.
The QT interval
is considered to be a surrogate of cellular action potential duration.
However, it yields a limited view of the complex electrogenesis of the
ventricular repolarization (VR). Evidence of T-wave end
inequality among surface ECG traces back to Wilson et
al,1 and it was recently revived by the concept
of dispersion.2 Because of its apparent
simplicity, QT dispersion became fashionable, and a growing literature
is now devoted to its potential prognostic interest. The study by Zabel
et al3 seems timely to temper the enthusiasm. In
a prospectively collected cohort of patients, it offers evidence that
avoiding technical biases of measurement, QT dispersion is not a
prognostic marker. This contrasts with the confirmation that ejection
fraction, heart rate variability, and simply heart rate are indeed good
predictors of events. It suggests some reflections about the correct
and comprehensive use of a concept that still needs to be
validated.
Technical Considerations
Measurement of QT Duration
The interexpert variation was expressed as 2 SD of the difference
between the median and the individual and final referee estimates. In
the P wave, the variation was 10.2 ms for the onset and 12.7 ms for the
offset. In QRS, it was 6.5 ms for the onset and 11.6 ms for the offset.
Compared with these values, the variation for the T-wave offset was
30.6 ms, with an intraindividual variability of 8 ms calculated from 3
readings of 26 ECGs.
Such a discrepancy in the manual QT duration measurement is not much of
a surprise. Improved homogeneity should be expected from automated
systems. Comparing some 19 systems, SDs as great as 30 ms were found
for the determination of the T-wave offset, compared with 6 ms for the
QRS onset.4 Thus, the approximation of QT
determination is of the same order of magnitude for man and machine. In
fact, the small but crucial improvement one can expect from a fully
automated system is its intrinsic 100% reproducibility. The problem is
not the intrasystem but the intersystem variability. At variance with
human evaluation, intersystem variations are more systematic, and
conceivably their discrepancies can be evaluated and compensated.
One might expect a better reproducibility in normal ECGs, but
this is not so.6 From 3-time measurements
performed by 2 observers, QT dispersion is highly nonreproducible, both
between subsequent recordings (25% to 35% relative error) and
between observers (28% to 33%). T-wave morphology contributes greatly
to the poor interobserver reproducibility. In 6 independent observers
of 30 ECGs, remarkable differences in the selection between 7
morphological categories were found, with a 30% to 40% interobserver
relative error in QT dispersion.7 Thus, complex
VR patterns probably explain the spectrum of values in the literature.
Kautzner et al7 conclude that "in the absence
of more objective criteria for separation of the T and U waves, the
measures of QT dispersion appear to be unstable and of questionable
statistical properties." We share their concerns.
QT Dispersion and Body Surface Mapping
In pathological T waves, any evaluation of their duration is further
complicated by their abnormal morphology. This applies to the long-QT
syndrome, in which De Ambroggi et al9 and then
Day et al2 started observations about augmented
QT dispersion. Sylven et al10 had already
compared normal subjects and patients with QT prolongation (>440 ms)
through 120 signal-averaged torso surface leads. Using return to
isoelectric line for T-wave end determination, interlead
QTc variability was 22% in normal subjects and
32% in patients (P<0.001). However, if a method was used
that discarded the leads in which U waves could not be identified from
the nadir between T and U, there was no longer any difference between
groups.
Theoretical Considerations
Fundamentals of Electrocardiography:
Appearance and Reality of QT Dispersion
The entire information about the ventricular electrical
activity is contained in a single image, the spatial QRS and T loops
that can be characterized by their morphology, planarity, speed, etc.
They can be projected on XYZ axes to form QRS-T complexes or on the
frontal, sagittal, and horizontal planes to display the loops of the
vectorcardiogram.
A single image like the spatial loop cannot generate any
"dispersion." Any projection of the loop implies the loss of a
part of the information, and looking at its dispersion in various
projections may be just a way to characterize the lost information.
Every time the tip of the vector progresses perpendicular to the axis
or to the plane, its projection becomes nil, as if the electrical
activity had disappeared. For instance, if during the last 40 ms
preceding the end of VR there is a positivity in lead II and an equal
negativity in lead I, according to Einthoven's equation the QT
duration in III will look 40 ms shorter in this lead. Therefore,
dispersion may be either an illusion or a reality, depending on the
conditions of recording. It is most probably an illusion in the
frontal plane, in which one cannot expect that a 2-lead
recording and 4 derived leads would actually provide any
information on local electrical activity. On the other hand, it
probably is a reality in the horizontal plane, in which the unipolar
leads V1 through V6 are
supposed to reflect the local activity. In theory, this applies only to
epicardial leads, and for QRS the intrinsic deflection defines the
moment of the local depolarization. An extrapolation is admitted for
pre- cordial leads with the label "intrinsecoid" rather than
intrinsic. Still, if these facts and concepts have been validated for
depolarization, the same does not apply to repolarization.
VR Process: Potential Mechanisms of QT Dispersion
Zabel et al14 found a significant
correlation (Pearson coefficient of 0.80) between the JT and QT
dispersion and the dispersion of action potential duration at 90%
repolarization and recovery time. This may suggest that the duration of
recovery is the factor that predominates over the spread of activation
in the genesis of QT dispersion. These authors also proposed new ECG
dispersion indexes, and one would easily agree that considering 2
extremes of QT is the simplest but somewhat simplistic approach of
dispersion. Our group proposed15 to consider
morphological aspects of the spatial T-wave loop to dissociate various
patterns contained in the entity of QT dispersion, a possibility if one
thinks of localized or diffuse VR abnormalities. Conventional QT
dispersion was significantly larger than in normal subjects in 2
pathological populations, namely, patients post myocardial infarction
and those with long-QT syndrome, that could not be discriminated in
this regard. Spatial T-wave loops extracted from XYZ data showed a loss
of planarity and an increased roundness in the 2 pathological groups.
The roundness was more pronounced in the infarcted group
(P=0.02) and the planarity more altered in the long-QT
syndrome (P=0.04). An interesting approach of morphology was
recently proposed,16 and apparently the
principal-component analysis applied to 12-lead
recordings adequately quantifies the VR complexity.
QT dispersion addresses macroscopic rather than microscopic
inhomogeneity. The potential interest of detecting susceptibility to
arrhythmias was highlighted some time
ago8 11 by use of the concept formulated by Han
and Moe.17 These authors, however, were referring
to inhomogeneity of recovery at the cellular level, and extrapolation
to ECG may not be adequate. In any case, the concept of inhomogeneity
and its implication in the term of dispersion can apply differently in
heart diseases as different as myocardial infarction,
cardiomyopathy, and long-QT syndrome. It remains to
be seen whether the existence of layers of M cells, in particular,
macroscopic areas,18 may help to fill the gap
between diffuse and localized
electrophysiological
disturbances.
Future of the Concept: Noninvasive Electrophysiology
The difficulty of measuring QT and the still not really defined
significance of QT dispersion explain why we are facing contradictory
conclusions concerning the prognostic value of this
parameter. During the period extending from the 1960s to
the present, conventional surface ECG was somewhat neglected, and
priority was given to invasive electrophysiology. We think that the
future of clinical electrophysiology resides in the ECG, on the
condition that we use it properly. We have to merge the computer
facilities now offered to the ECG and our better knowledge of
electrophysiology to develop noninvasive electrophysiology.
This process started successfully for the 2 first components of
the P-QRS-T complex and should continue with the third one. The P
component gives access to cardiac rate, and it is unnecessary to state
how heart rate and heart rate variability proved to be useful in
exploring the autonomic nervous system, a major component of cardiac
tachyarrhythmias. The QRS component forms the
arrhythmogenic substrate, and the detection of late potentials is the
noninvasive corollary of the invasive localization of earliest
depolarization. Analyzing the last milliseconds of the VR is probably
as important as scrutinizing the first milliseconds of depolarization.
The T wave is now quantifiable, and the morphology certainly is even
more important than the duration.19 It is not
really scientific to draw conclusions from a QT dispersion of >50 ms,
when the precision of the measurement simply approximates the same
order of magnitude. Just looking at this aspect of the problem,
however, it would be inappropriate to reject a good concept because of
the technical difficulties of its application.
Future of the Evaluation of VR
Another development may be to extend the notion of QT dispersion to QT
dynamicity, thus looking at the 2 dimensions formed by space and time.
QT dynamicity is to the T wave what heart rate variability is to the P
wave. QT dynamicity contains 2 important bits of information. The
behavior of the cellular action potential is reflected by QT
rate-dependence, and the autonomic nervous system modulates both QT
duration and rate-dependence. Studying QT dynamicity presupposes
selective manipulation of thousands of QRS-T complexes over 24 hours to
extract relevant information. This can be achieved, and in contrast to
the study of QT dispersion, the processing offers the definite
advantage of measuring changes of duration rather than absolute values.
Any algorithm can reliably detect changes on the order of the
millisecond simply because potential deviations from reference are
fixed. Our experience in the long-QT syndrome20
shows that QT dynamicity is a reliable marker of the probability of
events. If an alteration of the spatial distribution of VR indeed
exists in this syndrome, a dispersion of dynamicity, ie, a different
behavior of various regions, should be looked for because the
underlying phenomenon should logically have time as well as space
dimensions. More generally, any coincidence between different QT
duration and/or QT morphology (including QT alternans and postpause
changes) and/or dynamicity of VR would provide further evidence that
spatial dispersion is not an illusion but a reality and that
collecting, processing, and using the information properly would
further validate the concept.
Footnotes
The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
References
1.
Wilson FN, Macloed AG, Barker PS, Johnston FD.
Determination of the significance of the areas of the
ventricular deflections of the
electrocardiogram. Am Heart J. 1934;10:46–61.
2.
Day CP, McComb JM, Campbell RWF. QT dispersion: an
indication of arrhythmia risk in patients with long QT
intervals. Br Heart J. 1990;63:342–344.
3.
Zabel M, Klingenheben T, Franz MR, Hohnloser SH.
Assessment of QT dispersion for prediction of mortality or arrhythmic
events after myocardial infarction: results of a prospective long-term
follow-up study. Circulation. 1998;97:2543–2550.
4.
The CSE Working Party. A reference database for
multilead electrocardiographic computer measurement programs.
J Am Coll Cardiol. 1987;10:1313–1321.[Abstract]
5.
Willems JL, Abreu-Lima C, Arnaud P, van Bemmel JH,
Brohet C, Degani R, Denis B, Gehring J, Graham I, van Herpen G, Machado
H, Macfarlane PW, Michaelis J, Moulopoulos SD, Rubel P, Zywietz C. The
diagnostic performance of computer programs for the
interpretation of electrocardiograms. N Engl
J Med. 1991;325:1767–1773.[Abstract]
6.
Kautzner J, Gang Y, Camm AJ, Malik M. Short- and
long-term reproducibility of QT, QTc, and QT dispersion measurement in
healthy subjects. Pacing Clin Electrophysiol. 1994;17:928–937.[Medline]
[Order article via Infotrieve]
7.
Kautzner J, Gang Y, Kishore AGR, Copie X, Janota
T, Nagayoshi H, Camm AJ, Malik M. Interobserver reproducibility of QT
interval and QT dispersion in patients after acute myocardial
infarction. Ann Noninv Electrocardiol. 1996;1:363–374.
8.
Mirvis DM. Spatial variation of QT intervals in
normal persons and patients with acute myocardial infarction.
J Am Coll Cardiol. 1985;5:625–631.[Abstract]
9.
De Ambroggi L, Bertoni T, Locati E, Stramba-Badiale M,
Schwartz PJ. Mapping of body surface potentials in patients with the
idiopathic long QT syndrome. Circulation. 1986;74:1334–1345.
10.
Sylven JC, Horacek BM, Spencer CA, Klassen GA,
Montague TJ. QT interval variability on the body surface. J
Electrocardiol. 1984;17:179–188.[Medline]
[Order article via Infotrieve]
11.
Burgess MJ, Green LS, Millar K, Wyatt R, Abildskov JA.
The sequence of normal ventricular recovery. Am
Heart J. 1972;84:660–669.[Medline]
[Order article via Infotrieve]
12.
Franz MR, Bargheer K, Rafflenbeul W, Haverich A,
Lichtlen PR. Monophasic action potential mapping in human subjects with
normal electrocardiograms: direct evidence for the
genesis of the T wave. Circulation. 1987;75:379–386.
13.
Yuan S, Blomström-Lundqvist C, Pripp C-M, Pehrson
S, Wohlfart B, Olsson SB. Signed value of monophasic action potential
difference: a useful measure in evaluation of dispersion of
repolarization in patients with ventricular
arrhythmias. Eur Heart J. 1997;18:1329–1338.
14.
Zabel M, Portnoy S, Franz MR. Electrocardiographic
indexes of dispersion of ventricular repolarization: an
isolated heart validation study. J Am Coll Cardiol. 1995;25:746–752.[Abstract]
15.
Badilini F, Fayn J, Maison-Blanche P, Leenhardt A,
Forlini MC, Denjoy I, Coumel P, Rubel P. Quantitative aspects of
ventricular repolarization: relationship between
three-dimensional T wave loop morphology and scalar dispersion.
Ann Noninv Electrocardiol. 1997;2:146–157.
16.
Priori SG, Mortara DW, Napolitano C, Dielh L, Paganini
V, Cantù G, Schwartz PJ. Evaluation of the spatial aspects of
T-wave complexity in the long-QT syndrome. Circulation. 1997;96:3006–3012.
17.
Han J, Moe GK. Nonuniform recovery of excitability.
Circulation. 1964;14:44–60.
18.
Sicouri S, Antzelevitch C. A subpopulation of cells
with unique electrophysiological properties
in the deep subepicardium of the canine ventricle. Circ Res. 1991;68:1729–1741.
19.
Merri M, Benhorin J, Alberti M, Locati E, Moss AJ.
Electrocardiographic quantitation of ventricular
repolarization. Circulation. 1989;80:1301–1308.
20.
Neyroud N, Maison-Blanche P, Denjoy I, Chevret S,
Guicheney P, Fayn J, Badilini F, Schwartz K, Coumel P.
Diagnostic performance of QT interval variables
from 24-hour electrocardiography in the long QT
syndrome. Eur Heart J. 1998;19:158–165.
© 1998 American Heart Association, Inc.
Editorials
Dispersion of Ventricular Repolarization
Reality? Illusion? Significance?
Key Words: Editorials • ventricles • electrophysiology
QT interval can be measured manually or with dedicated algorithms.
The performances of the 2 approaches were compared in a
remarkable study conducted by the late Jos
Willems.4 The aim was to assess the
diagnostic performances of computerized
systems.5 In view of the interobserver and
intraobserver variability in determining wave recognition points, an
elaborate reviewing scheme was devised to obtain a group estimate that
should define the "truth," ultimately serving as a standard for
computer measurement. Five experts defined individually the P- and
QRS-wave onset and offset and the T-wave offset. The database was
formed of 250 digitized (500 Hz) 12 standard leads and Frank XYZ leads,
including a 25% proportion of normal hearts and a variety of
ventricular hypertrophies and infarctions but no
bundle-branch block or long-QT syndrome.
Evaluation of QT dispersion from the 12-lead ECG is a
surrogate of body surface QRST integral mapping, an approach that
offered somewhat overlooked although important contributions.
Mirvis8 used 150 electrodes in 50 subjects and
measured QT intervals automatically. The QT dispersion, a term not yet
coined at the time, was 59.4±12.9 ms. Formulating the results in terms
of absolute shortest (384±40 ms) and longest (414±30 ms) QT values
was, in fact, more informative to express the difference between normal
subjects and patients with infarcts. In anterior infarcts (n=15), there
was a significant prolongation of the longest QT intervals (476±32 ms)
and no difference in the shortest. The same applied to
inferior infarcts, and interestingly, the distribution of
the longest QT intervals differed according to the infarct location,
thus suggesting that there was indeed some information on the spatial
distribution of VR.
Not only is QT dispersion difficult to measure, but its
significance is also poorly understood. Some basic notions of
electrocardiography and electrogenesis should
be recalled. Thus, the information contained in limb leads is
redundant. If any 2 of the 6 are recorded, the other 4 can be
derived according to Einthoven's equation (III=II-I) and to the
relationships between bipolar and unipolar leads (I=VL-VR, II=VF-VR,
and III=VF-VL). This by no means implies that QT duration cannot be
different in all 6 leads, for the reasons expressed below.
The timing of VR termination in a given point results from
the combination of 2 factors one cannot dissociate in surface ECG: the
timing of activation and the local duration of recovery. The latter can
be explored by measuring the refractory periods11
and/or recording monophasic action
potentials.12 The action potential duration tends
to be shorter at the epicardium and basal regions and longer at the
endocardium and apex. Conceivably, the 2 factors can compensate for
each other, and a delayed activation with a shorter action potential
may give the same QT interval as a normally activated zone with
a prolonged action potential. Yuan et al13
proposed to dissociate the 2 factors by combining the information
obtained from QRS and the monophasic action potential.
The evaluation of VR must be improved. Technically, only digitized
recordings should be considered, a necessity that occasionally
would favor prospective studies. A decisive advantage of computer
techniques is a reproducible deviation from the humanly defined
reference.4 5 An adequate quantification of the
QT dispersion would probably help to better understand its significance
through its pathophysiological variations, on the
condition that we get rid of nonrelevant information based on
redundance and illusion. There is no doubt that resurgence of QRST
integral mapping would be suitable, although this technique obviously
suffers from practical limitations in its clinical applications.
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