Risk markers used in conjunction may improve prediction of sudden cardiac death

Microvolt T-wave alternans and electrophysiologic study identified distinct arrhythmogenic substrates that, when used in conjunction, were shown to better predict the complex electroanatomic substrates underlying sudden cardiac death risk.

The study included 566 patients with ischemic cardiomyopathy from the Alternans Before Cardioverter Defibrillator trial. Participants had a left ventricular ejection fraction ≤0.40 and nonsustained ventricular tachycardia. All patients underwent electrophysiologic study and microvolt T-wave alternans testing.

Researchers reported 28 stable ventricular tachyarrhythmic events and 10 unstable ventricular tachyarrhythmic events. Microvolt T-wave alternans were predictive of unstable ventricular tachyarrhythmic events (event rate 2.7% in abnormals vs. 0% in normals), whereas electrophysiologic study was not predictive (1.5% vs. 3.2%). Conversely, electrophysiologic study predicted stable ventricular tachyarrhythmic events (9.7% vs. 2.2%), but microvolt T-wave alternans did not predict them (5.5% vs. 4.4%). Although the extent of LV contractile dysfunction alone (LVEF ≤0.30 vs. LVEF ≥0.31) did not predict events, microvolt T-wave alternans predicted events better than electrophysiologic study in patients with LVEF ≤0.30. In contrast, electrophysiologic study predicted events better than microvolt T-wave alternans in patients with LVEF >0.30.

“Our data strongly suggest that combining multiple risk markers, rather than using LVEF alone, will capture some of the complexity associated with the risk of sudden cardiac death,” the researchers concluded. “These data can serve as a basis for future randomized studies using combinations of risk markers to identify patients at highest risk of sudden death.”

One of the main interests of the study, wrote Sandeep V. Pandit, PhD, of the Center for Arrhythmia Research, University of Michigan in Ann Arbor, in an accompanying editorial, was the question of why a stable arrhythmia is typically the outcome of an electrophysiologic study test, whereas a T-wave alternans test leads to unstable arrhythmias in patients with ischemic cardiomyopathy.

“The results,” Pandit wrote, “… suggest that clinical trials with a larger cohort of patients and longer duration are needed in order to assess whether the T-wave alternans test can increase our ability to identify patients at risk for arrhythmogenesis and to distinguish between varied arrhythmogenic substrates.”

Amit G. Heart Rhythm. 2010;7:763-768.

Amit and colleagues address the important problem of risk stratification for patients who are candidates primary prevention of sudden cardiac death by an implantation of an ICD. Although microvolt T-wave alternans testing has been shown to have utility, it has not gained widespread acceptance despite positive clinical trial data. The present study suggests that microvolt T-wave alternans and electrophysiologic study identify distinct arrhythmogenic substrates: microvolt T-wave alternans testing is predictive of unstable ventricular tachyarrhythmia events especially in patients with a LVEF ≤0.30, whereas electrophysiologic study is predictive of stable ventricular tachyarrhythmia events in patients with a LVEF >0.30. However, at the end of the day, doing tests other than measurement of the LVEF takes time, and the current climate is not one conducive to finding reasons to not implant an ICD. Furthermore, it is unlikely that finding a risk for any ventricular tachyarrhythmia events, even a "stable" one, in a patient with a between LVEF 0.30 and 0.40 will dissuade an electrophysiologist from implanting an ICD especially since "stability" was defined by monomorphic ECG morphology and not hemodynamics. What we need to withhold implantation is a virtually perfect test that predicts the absence of any ventricular tachyarrhythmia events before risk stratification can realistically be adopted. That dream has yet to be achieved.

– Andrew E. Epstein, MD

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