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Clinical Studies

The first major study of MTWA was published in the New England Journal of Medicine in 1994 and concluded that MTWA was an independent marker of arrhythmic vulnerability equivalent to invasive electrophysiology testing. Since that time, several large‐scale studies have confirmed the predictive value of MTWA in various patient groups including those with left ventricular dysfunction, ischemic cardiomyopathy, non‐ischemic cardiomyopathy and history of myocardial infarction.

A 2009 meta‐analysis of 13 studies (~6,000 pts) showed that patients with an abnormal MTWA result are up to 14 times more likely to experience sudden cardiac arrest than those with a normal test result. This analysis also concluded that a negative MTWA test confers an extremely low risk of experiencing SCA in the next 12‐18 months (<0.3%).

The ACC/AHA/ESC clinical guidelines list MTWA testing as Class IIa with the highest level of evidence (A).

Key MTWA studies are included in the table below. Download a complete bibliography.

AuthorTitleSummary
Wita et al, Adv Med Sci (2012) Microvolt T-wave Alternans Predicts Cardiac Events after Acute Myocardial Infarction in Patients Treated with Primary Percutaneous Coronary Intervention

"Our findings suggest that the MTWA test is a powerful predictor for a combined endpoint including not only mortality but also worsening of heart failure and defines a high-risk subgroup."
Sredniawa et al, Kardiologia Polska (2012) Microvolt T-Wave Alternans and Other Noninvasive Predictors of Serious Arrhythmic Events in Patients with an Implanted Cardioverter-Defibrillator "The most important finding of our study was that abnormal MTWA was demonstrated to be an independent risk factor for [major arrhythmic cardiac events] following ICD implantation."
Merchant et al., Heart Rhythm (2012) Clinical Utility of Microvolt T-wave Alternans Testing in Identifying Patients at High or Low Risk of Sudden Cardiac Death “In patients without ICDs, MTWA testing is a powerful predictor of SCD. Among patients with LVEF ≤ 35%, a negative MTWA test is associated with a low risk for SCD. Conversely, among patients with LVEF > 35%, a positive MTWA test identifies patients at significantly heightened SCD risk.”
Merchant et al., Circ (2012) Role of Substrate and Triggers in the Genesis of Cardiac Alternans, From the Myocyte to the Whole Heart "In the present report we have attempted to present a novel framework for how an 'appropriate' substrate and an 'appropriate' trigger event may synergistically contribute to the mechanisms that generate cardiac alternans from the cellular to the whole-heart level, and we propose novel aspects of the use of [MTWA] to guide therapy."
Shizuta et al., Clin Res Cardiol (2011) Prognostic Utility of T-Wave Alternans in a Real-World Population of Patients with Left Ventricular Dysfunction: The PREVENT-SCD Study "The event-free rate for severe ventricular tachyarrhythmic events in TWA-negative patients was excellent, 100% at 1 year, 98.6% at 2 years, and 97.0% at 3 years."
Hohnloser et al., Heart Rhythm (2009) Evidence Regarding Clinical Use of Microvolt T-wave Alternans “This study found that MTWA testing using the spectral analytic method provides an accurate means of predicting [ventricular tachyarrhythmic events] in primary prevention patients without implanted ICDs; in particular, the event rate is very low among such patients with a negative MTWA test.”
Costantini et al., JACC (2009) The ABCD (Alternans Before Cardioverter Defibrillator) Trial: Strategies Using T-Wave Alternans to Improve Efficiency of Sudden Cardiac Death Prevention “The ABCD study is the first trial to use MTWA to guide prophylactic ICD insertion. Risk stratification strategies using noninvasive MTWA versus invasive EPS are comparable at 1 year and complementary when applied in combination. Strategies employing MTWA, EPS, or both might identify subsets of patients least likely to benefit from ICD insertion.”
Salerno-Uriarte et al., JACC (2007) Prognostic Value of T-Wave Alternans in Patients With Heart Failure Due to Nonischemic Cardiomyopathy: Results of the ALPHA Study “Among NYHA functional class II/III nonischemic cardiomyopathy patients, an abnormal TWA test is associated with a 4-fold higher risk of cardiac death and life-threatening arrhythmias.”
Bloomfield et al., JACC (2006) Microvolt T-Wave Alternans and the Risk of Death or Sustained Ventricular Arrhythmias in Patients With Left Ventricular Dysfunction “Among patients with heart disease and LVEF ≤ 0.40, MTWA can identify not only a high-risk group, but also a low-risk group unlikely to benefit from ICD prophylaxis.”
Chow et al., JACC (2006) Prognostic utility of Microvolt T-wave Alternans in Risk Stratification of Patients with Ischemic Cardiomyopathy “Microvolt T-wave alternans is a strong and independent predictor of all-cause and arrhythmic mortality in patients with ischemic cardiomyopathy.”
Ikeda et al., JACC (2006) Predictive Value Of Microvolt T-Wave Alternans for Sudden Cardiac Death in Patients With Preserved Cardiac Function After Acute Myocardial Infarction: Results of a Collaborative Cohort Study “In patients with preserved cardiac function, the incidence of indeterminate results of microvolt TWA is low, and a positive test result is associated with arrhythmic events.”