MMA Method

Editor Comments

D. Marangoni

www.alternans.org

The main problem of the MMA method is that there is no established criteria for interpretation ( no prospective clinical paper using a predetermined criteria ) and each new paper is using a new cutpoint for interpretation ( 5 different cutpoints in 5 different papers). In all the MMA clinical trials a retrospective analysis was done and therefore it is impossible to use the MMA method clinically for risk assessment of Sudden Death :

In Nieminen et al (1), five alternans cutpoints and two update factors were evaluated. The optimal combination in this study was found to be a cutpoint of 65 mV with an update factor of 1/8. To establish the validity of these parameters, they must be prospectively tested in a similar patient population. This is particularly important for MMA-TWA, since previous cutpoints reported in the literature are not consistent with these values (2-5).

In study of 322 post-MI patients, Exner et al report an MMA-TWA cutpoint of 5.0 mV after subtraction of noise, when measured immediately post-exercise (4).

In a study of 41 patients with LV dysfunction, Cox et al found an optimal cutpoint of 10.75 mV using receiver-operating characteristics (2). Even with this optimal cutpoint, however, the predictive value of TWA measured with the MMA method was not statistically significant.

In a retrospective analysis of 44 post-MI patients from the ATRAMI database, the value associated with the 75^th percentile of the control group was used as the cutpoint and was lead-specific (46.6 mV in lead V1 versus 53.0 mV in lead V5) [5].

In a study of 23 ICD patients and 17 controls (3), Kop et al report that changes in MMA-TWA with mental stress and bicycle exercise were greater in the ICD group. While the magnitude of the stress-induced changes in MMA-TWA were noted, absolute values were not reported and the authors did not suggest optimal cutpoint values for discrimination.

An evaluation of these studies in the aggregate illustrates that there is no consensus on the optimal cutpoint for positivity of an MMA-TWA test. In addition, the FDA documentation for the GE MMA-TWA system does not provide guidelines for interpretation; indications for use state that the system “is intended to provide only the measurements of the fluctuations of the ST-T wave…No interpretation is generated [510(k) #K032513].”

1. Nieminen, T., et al., T-wave alternans predicts mortality in a population undergoing a clinically indicated exercise test. Eur Heart J, 2007

2. Cox, V., et al., Predicting arrhythmia-free survival using spectral and modified-moving average analyses of T-wave alternans. Pacing Clin Electrophysiol, 2007. 30(3): p. 352-8.

3. Verrier, R.L., et al., Ambulatory electrocardiogram-based tracking of T wave alternans in postmyocardial infarction patients to assess risk of cardiac arrest or arrhythmic death. J Cardiovasc Electrophysiol, 2003. 14(7): p. 705-11.

4. Exner, D.V., et al., Noninvasive Assessment of Sudden Death Risk After Myocardial Infarction - Results of the REFINE Study. Heart Rhythm, 2007. 4(5): p. S94.

5. Kop, W.J., et al., Effects of acute mental stress and exercise on T-wave alternans in patients with implantable cardioverter defibrillators and controls. Circulation, 2004. 109(15): p. 1864-9.