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T wave alternans (TWA), defined as a consistent
beat-to-beat variation of the T wave morphology and/or polarity during sinus rhythm, has
been shown to be associated with a with ventricular arrhythmias in acute myocardial
ischaemia and infarction, stable coronary artery disease, prolonged QT syndrome and
dilated cardiomyopathy2. It is postulated that
ischaemia induced alternation in action potential morphology, dispersion of repolarisation
and changes in recovery of excitability may play an important role in both the
susceptibility to ventricular fibrillation and the genesis of TWA4,5.
Recently, microvolt TWA measured during atrial pacing (spectral analytical method), has
been associated with the inducibility of sustained ventricular tachycardia (VT) or
ventricular fibrillation (VF) during electrophysiology testing5.
The non-invasive assessment of exercise induced TWA in patients with a history of
ventricular tachyarrhythmias has been shown to be comparable to the results of atrial
pacing in predicting ventricular vulnerability6,7.
In a pilot study of 64 patients (48 male, age 33 ± 12 years) with hypertrophic
cardiomyopathy, seven of whom had documented episodes of sustained ventricular tachycardia
and/or ventricular fibrillation, exercise-induced TWA was highly associated with a history
of VT/VF events (sensitivity 100%, specificity 53%, p < 0.01)8.
More recently, we have assessed microvolt TWA in 168 patients with HCM and 15 patients
with hypertension (unpublished data). In this study patients were considered to be at high
risk of SCD if they had been successfully resuscitated after documented sustained VT
and/or VF arrest or had two or more of the established risk factors for SCD.
Exercise-induced microvolt TWA was significantly associated with a high risk of SCD: 78%
of patients at low risk (< 1 risk factor for SCD) had negative TWA and 58% of
patients at high risk of SCD (< 2 risk factors for SCD) had positive TWA. Table
I demonstrates the predictive value of TWA for patients with two or more risk factors for
SCD. In this study, the combination of TWA with any of the established risk factors for
SCD (FHSCD, SYN, FBP and NSVT) improved the sensitivity and positive predictive accuracy
for SCD. Table II demonstrates the relation of TWA to established risk factors for the
prediction of VT/VF events in 11 patients with a history of cardiac arrest. In the small
cohort of patients with essential hypertension and no history of coronary artery disease
and ventricular arrhythmias were also studied, 81% of them had negative TWA scores,
supporting the hypothesis that myocardial disarray and extensive fibrosis, which are not
usually seen in patients with hypertension but are characteristic findings in HCM,
contribute to the dispersion of repolarisation and inhomogeneity of ventricular
refractoriness that probably causes TWA. A limitation of this study was that thirty-six
per cent of patients had "indeterminate" TWA scores during exercise due to
frequent ectopic beats and increased level of noise created by interference signals from
motion artefact (breathing, pedalling). Recently, new noise reduction techniques have been
utilised to compute alternans, in particular the upgrading of software to differentiate
between artefactual and physiologic alternans, and the use of continuous measurement of
electrode impedance to reduce the artefact resulting from movement.
Table I - Predictive value of TWA for patients with two or more risk factors for
sudden cardiac death
Sens.
|
Spec.
|
PPV
|
NPV
|
p
|
55%
|
63%
|
39%
|
76%
|
0.03
|
Sens. = sensitivity; PPV = positive predictive value; Spec. =
specificity; NPV = negative predictive value.
Table II - The sensitivity and positive predictive value of TWA for VT/VF events in
relation to established risk for sudden cardiac death
|
FHSCD
|
SYN
|
AbnBP
|
NSVT
|
risk factor
Sensitivity
Pos. pred. value
p value
|
30
5
0.7
|
36
13
0.7
|
60
16
0.02
|
63
14
0.02
|
risk factors + twa
Sensitivity
Pos. pred. value
p value
|
57
14
0.01
|
43
20
0.03
|
71
25
0.0001
|
43
17
0.01
|
FHSCD = family history of premature sudden cardiac death; NSVT =
nonsustained ventricular tachycardia; AbnBP = flat or hypotensive blood pressure response
on exercise; SYN = syncope; TWA = T wave alternans; Sens. = sensitivity; Pos. pred. value
= positive predictive value.
p value is based on chi square analysis of individual risk factors in patients with and
without history of cardiac arrest.
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