CORRESPONDENCE: LETTER TO THE EDITOR
Microvolt T-Wave Alternans: Where Do We Go From Here?
Paul S. Chan, MD, MSc*,
Brahmajee K. Nallamothu, MD, MPH and
Theodore Chow, MD, FACC
* Cardiology (111-A), University of Michigan, 2215 Fuller Road, Ann Arbor, Michigan 48105 (Email: paulchan{at}umich.edu).
The recent meta-analysis by Gehi et al. (1) assessed the value of microvolt T-wave alternans (MTWA) testing to predict cardiac arrhythmic events in differing patient populations. Their analyses provide a summary estimate of the predictive value of MTWA in patients with ischemic and non-ischemic cardiomyopathy. In their discussion, the investigators point out that while MTWA has shown promise in identifying high-risk patients, studies have been hampered by small sample sizes. Importantly, this has limited the comparisons of baseline characteristics between individuals with negative and non-negative MTWA tests in most studies and has prevented adequate multivariable adjustment for potential confounders.
This raises questions as to whether MTWA is simply a surrogate marker of patients with greater disease burden and severity. If so, differences in age, left ventricular ejection fraction (LVEF), clinical comorbidities, and medication treatment between individuals with negative and non-negative MTWA tests may explain its predictive power. We believe that in order for MTWA to gain wider acceptance as a risk stratification tool, three types of analyses are needed. First, multivariable modeling that adjusts for demographics, LVEF, clinical comorbidities, medication treatment, as well as electrophysiologic variables (e.g., Holter monitoring, QRS duration, electrophysiologic study) should be done to show that MTWA is an independent predictor of cardiac arrhythmias. Gehi et al. (1) themselves acknowledge that MTWA does not offer incremental prognostic utility unless it can be shown to add predictive power beyond known risk factors for cardiac arrhythmia (such as LVEF in patients with ischemic cardiomyopathy).
Second, studies of MTWA should provide analyses of all-cause mortality in addition to arrhythmic mortality. Prior studies of MTWA that used a primary end point of cardiac arrhythmic events may be limited as they did not consider competing risks whereby MTWA may predict arrhythmic, but not all-cause, mortality.
Finally, even if future studies demonstrate that MTWA offers incremental prognostic utility in assessing high-risk patients, its true utility for risk stratification will only be known when the mortality reduction benefit of implantable cardioverter-defibrillators (ICDs) is evaluated in patients who test MTWA-negative and non-negative. This could be accomplished by randomizing patients to ICD therapy after MTWA testing, but such a clinical trial might raise ethical concerns given that some high-risk patients may be denied life-saving therapy. To justify such a clinical trial, additional cohort analysis using propensity scores for ICD therapy based on MTWA status may be needed (2).
Gehi et al. (1) are to be commended for their synthesis of a large pool of clinical data on MTWA. Future studies of MTWA should focus on its incremental prognostic utility after multivariable adjustment, but ultimately the true utility of MTWA in risk-stratifying high-risk patients will remain uncertain unless it can be shown that the benefit of ICDs differs by MTWA subgroup.
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1. Gehi AK, Stein RH, Metz LD, Gomes JA. Microvolt T-wave alternans for the risk stratification of ventricular tachyarrhythmic eventsa meta-analysis. J Am Coll Cardiol 2005;46:75-82.[Abstract/Free Full Text]2. Chan PS, Hayward RA. Mortality reduction by implantable cardioverter-defibrillators in high-risk patients with heart failure, ischemic heart disease, and new-onset ventricular arrhythmiaan effectiveness study. J Am Coll Cardiol 2005;45:1474-1481.[Abstract/Free Full Text]
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