Editorial: New MTWA studies on ICD patients, end points, follow up time, indeterminate results and MTWA Stress /EP protocols.
Very recently, new MTWA studies in ICD patients have reported very interesting
results on MTWA test capability regarding the selection of ICD patients who
will benefit from ICD implantation. However, some results of these ICD studies
need to be discussed in greater detail. Thus, I believe that it is important to
discuss the possible reasons for these results in order to learn, how to
improve MTWA tests and avoid technical pitfalls.
T. Chow (1) in a population of 768 patients of which 51% received ICD
has shown that ICD were associated with lower mortality in MTWA non-negative
patients but not in MTWA negative patients suggesting the need to use MTWA to
select these patients. In the same population T. Chow (2) has also shown that
in non ICD Cohort the discrimination between MTWA negative and non negative was
better than in the ICD Cohort.
In the ABCD study presented at AHA 06, most of patients had ICD
implanted and MTWA has shown good predictive value in the first 12 months but
lower predictive value in the following 12 months (ICD shocks were included in
the endpoints). In the SCD-Heft TWA observational sub-study presented at AHA 06
in 490 patients enrolled in 37 sites (mean 4 patients/site/year) the number of
indeterminate test were 41% and the end points were including ICD shocks.
In the past the typical endpoints of most MTWA papers have been :
Sustained Ventricular Tachycardia +VF ,
VF + Sudden Death or Total
Mortality. Now due to the availability of Clinical data that include ICD
discharges it is important to know that ICD discharge is
an unreliable endpoint. Of
the three patients who have ICD shocks, only one would have otherwise died
suddenly (3). A negative MTWA test
eliminates patients with lethal arrhythmias, but not patients with non-lethal
VT (maybe it doesn't for example identify RVOT VT -Right Ventricular Outflow
Tract Tachycardia - which is almost never
fatal). In studies in which MTWA was
used to predict cardiac arrest or SCD, there are essentially no events among
those who test negative (4).
In most studies the follow up is
18-24 months (5). In some studies having a low event rate, the investigators,
trying to collect more end points, have extended this time up to 52 months (5).
It is clear that the arrhythmogenic substrate can change over time and a follow up of more than 18 months
can be unreliable. Most experts suggest
to retest a risky patient every 12-18 months.
The average number of indeterminate
results in most papers, is in the rage 15-25%. Indeterminate results can be
due to ectopic beats, failure to reach target HR, un-sustained Alternans (6). Technically
inadequate tests depends from too high HR rise, muscular noise due to
Electrodes/Sensors positioning (not on the bones) and patient cooperation
(upright position and no hand grip). Indeterminate results depends also from
the population selection i.e. 5% in athletes population and experience to run a
test to reach the target HR without increasing too much patient muscular noise:
an experience trained Centre with more than 2 tests per week usually have
indeterminate results less than 20%. Retesting a patient with indeterminate
results can reduce indeterminate results by 50% (7). A MTWA Centre training
requires at least one full day training and a follow up with review of the MTWA tests reports from an expert reader
who could suggest improvements in handling the test. Withdrawal
of a Beta-blocker medication for the day of the test can help in reducing
indeterminate results due to failure to
reach target HR.
The earliest
suggested Stress Test protocols were aimed at reaching a stable HR > 105 for
more than 3 minutes. Anyhow, sometime Alternans appeared in the range of 105-110
bpm and some patients were not pushed to reach 110 bpm (by definition a test is
considered positive if sustained alternans has an onset HR =< 110) so more
precise protocols were suggested to reach an HR of 110. The latest protocol
suggests to keep the HR stable in the range 100-110 for more than 2, 5
minutes and over 110 bpm for 1, 5 minutes to enable the detection of a
Sustained Alternans appearing near 110 bpm. Some Clinical studies started many
years ago so the protocol used was not the latest one. Many Technically
Inadequate tests were due to old Stress protocols. Also the latest EP protocols
suggest keeping HR stable at 110 for 5
minutes (A-pace). If 1:1 conduction is not achieved,
then AV sequential pacing with an AV-delay of 180 ms is recommended for 5
minutes, because Alternans is stable only after some minutes after pacing at 550
msec.
REFERENCES
1.
Chow T.
Microvolt T-Wave Alternans Identifies Patients With Ischemic Cardiomyopathy Who
Benefit From Implantable Cardioverter-Defibrillator Therapy ( J Am Coll
Cardiol, 2007;49:50-58)
2. Chow T. Prognostic Utility
of Microvolt T-Wave Alternans in Risk Stratification of Patients With Ischemic
Cardiomyopathy (J Am Coll Cardiol 2006;47:1820-7)
3. Germano
J. Frequency and Causes of Implantable Cardioverter-Defibrillator Therapies: Is
Device Therapy Proarrhythmic? (Am J Cardiology 2006;97:1255-1261
4.
Ikeda T.
T-Wave Alternans as a Predictor for Sudden Cardiac Death After Myocardial
Infarction (Am J Cardiology 2002 ;89: 79-82)
5.
Gehi A.
Microvolt T Wave Alternans for the Risk Stratification of Ventricular
Tachyarrhythmic Events. A Meta-Analysis (J Am Coll Cardiol 2005;46:75-82)
6.
Kaufman E.
“Indeterminate” Microvolt T Wave Alternans Tests Predict High Risk of Death or
Sustained Ventricular Arrhythmias in Patients with Left Ventricular
Dysfunction. (J Am Coll Cardiology 2006; 48:1399-1404)
7.
Chow T.
Clinical value of repeating indeterminate MTWA test (abst). Am Coll Cardiol
2005;45:93A