T-wave alternans test's prognostic horizon exceeds two years in analysis

July 22, 2008 | Steve Stiles  (The Heart.org)

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Kansas City, MO and Cincinnati, OH - The power of the microvolt T-wave alternans (mTWA) test in stratifying patients with ischemic cardiomyopathy for risk of sudden cardiac death as part of the screening of candidates for an implantable cardioverter-defibrillator (ICD) remains significant over a horizon of up to three years, according to an analysis from one of the technique's most experienced groups [1].

The finding sheds light on a persisting question about the mTWA test: how often should it be performed in patients with a negative result but who remain eligible for ICDs based on LVEF criteria?

"Although it makes intuitive sense that the predictive value of a screening test in such a high-risk population wanes over time, our findings suggest that mortality and arrhythmic risk with a nonnegative mTWA test result remain robust through the first two to three years," write the authors in the August 1, 2008 issue of the American Journal of Cardiology.

By convention, nonnegative mTWA tests include those that either show mTWA or are indeterminate.

"At least in this cohort, there didn't seem to be any huge fall-off in the test's discriminatory power at a follow-up of two to three years," lead author Dr Paul S Chan (St Luke's Mid America Heart Institute, Kansas City, MO) told heartwire. He and his colleagues propose that retesting every two years might be adequate. "Now, this is the first time that this has been looked at in this way, so it definitely needs to be validated in other cohorts, and it should be looked at in a prospectively designed study as well."

The post hoc analysis looked at a cohort in which a baseline mTWA test had previously been shown to stratify sudden-death risk over an average of 18 months [2], as reported by heartwire at the time. It included 768 patients with ischemic heart disease and an LVEF <35% but no history of sustained ventricular arrhythmias.

About 60% of the patients were implanted with ICDs; the analysis controlled for that as well as demographics, LVEF, ECG parameters, medications, and comorbidities.

A nonnegative baseline mTWA test was associated with more than double the adjusted cumulative risk of all-cause death or appropriate ICD discharge six months later and at intervals of six months out to three years.

Hazard ratio for all-cause mortality and appropriate ICD shocks by six-month intervals after a nonnegative mTWA test

Months follow-up

HR (95% CI)

p

6

2.49 (0.93-6.66)

0.07

12

2.21 (1.11-4.40)

0.02

18

2.22 (1.24-3.98)

0.008

24

2.60 (1.48-4.56)

<0.001

30

2.43 (1.45-4.07)

<0.001

36

2.37 (1.47-3.84)

<0.001

With the test showing no apparent decrease in predictive power over three years, the group looked at risk at intervals of one, two, and three years, with hazard ratios reflecting noncumulative risk during each specified 12-month period. The risk of all-cause death or appropriate shock was doubled in the first year, more than tripled in the second, and trended higher in the third year.

"We didn't expect it to have significant statistical power year by year," Chan said. A more important observation, he emphasized, is that statistical tests for interaction among the year intervals showed no significant variations, suggesting there is little meaningful change in the test's prognostic power at one, two, and three years.

Hazard ratio for all-cause mortality and appropriate ICD shocks by year intervals after a nonnegative mTWA test

Follow-up year

HR (95% CI)

p

0-12 mo

2.19 (1.10-4.34)

0.03

>12 to 24 mo

3.36 (1.28-8.83)

0.01

>24 to 36 mo

2.06 (0.81-5.22)

0.13

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With the analysis confined to a specific patient cohort, Chan observed, questions remain about the mTWA's predictive power in different populations. He pointed, in particular, to the MASTER 1 trial, which—as previously covered by heartwire—questioned the test as a risk stratifier in a population of patients with ischemic heart disease and an LVEF <30%, all of whom had been implanted with ICDs.

The study was partly funded by Medtronic.