Editorial: New MTWA studies on ICD patients, end points, follow up time, indeterminate results and MTWA Stress /EP protocols.


D. Marangoni, Editor of Alternans.org



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.


New MTWA ICD Studies


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.



ICD shock as End Point


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).


Follow up time


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.



Indeterminate and technically inadequate tests


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.


MTWA Stress/ EP Protocols


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.




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