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Microvolt T-wave Alternans: Useful in Predicting ICD Need?
Abstract & commentary
By John P. DiMarco, MD, PhD
Source: Costantini O, et al. The ABCD (Alternans Before Cardioverter Defibrillator) trial. strategies using T -wave alternans to improve efficiency of sudden cardiac death . J Am Coll Cardiol. 2009;53:471-479.
The clinical utility of microvolt T-wave alternans (MWTA) testing to detect subtle beat-to-beat oscillations in the electrocardiogram's T-wave amplitude as a non-invasive method for predicting sudden cardiac death remains undetermined. In this study, Constantini et al report a multi-center trial in which patients being considered for ICD implantation underwent both MTWA testing and electrophysiologic studies (EPS) with programmed stimulation to compare the predictive accuracy of the two methods. Patients were eligible for enrollment if they had a left-ventricular ejection fraction £ 40% and non-sustained ventricular tachycardia documented by 24-hour ambulatory ECG recordings within six months of enrollment. All patients underwent both MTWA testing and EPS using a standard ventricular stimulation protocol. The results of MTWA tests were classified as positive, indeterminant, or negative. EPS was considered positive if sustained, monomorphic ventricular tachycardia was induced with any part of the protocol, or if ventricular fibrillation was induced with one or two extrastimuli. ICD insertion was mandated in all patients with either a positive MTWA or EPS results. In patients with MTWA indeterminate, or both tests negative, investigators could elect not to implant a device. ICD programming was standardized for detection of ventricular arrhythmias exceeding 171 bpm, with shock-only therapy at maximum outputs.
The primary endpoint for the study was defined as either the first appropriate ICD discharge or sudden cardiac death during the first year of follow-up. Events were classified by an independent committee blinded to the results of the testing. The study was designed as a noninferiority comparison of the positive and negative predictive values of MTWA and EPS.
The study population included 566 patients who underwent both EPS and MTWA tests for risk stratification. For the entire group, the mean age was 65 years; 84% were male. Eighty-one percent of the patients were New York Heart Association functional class I or II. The mean left-ventricular ejection fraction was 28%. The group included 77 patients who had an ejection fraction between 0.36 and 0.40 and, therefore, would have a current indication for an ICD implant only if they were EPS positive. Patients were on stable medical therapy, including an ACE inhibitor or angiotensin receptor blocker in 89%, a beta blocker in 86% and a statin in 81%. The MTWA test was positive, negative, and indeterminant in 46%, 29%, and 25% of the patients, respectively. The EPS was positive in 40%. Ninety-seven percent of patients who were either MTWA positive or EPS positive received ICDs. ICDs were implanted in 67% of patients with a negative or indeterminant MTWA result and a negative EPS and in 100% of those patients with a negative MWTA result and a positive EPS. During follow-up, the overall one- and two-year event rates were 7.5% and 14%, respectively. There were 55 appropriate ICD discharges and 10 sudden cardiac deaths.
As shown in Table 1, patients who were both MTWA- and EPS-negative had the lowest 12-month event rate (2.3%). Patients who were both MTWA-positive or indeterminant and EPS-positive had the highest one-year event rates (11.1% and 14.8%, respectively). At two years, however, both tests didn't perform as well. Even MTWA-negative and EPS-negative patients had a 24-month event rate of 10.1%. The two-year event rates in the four groups with one or another test positive or negative, ranged from 14%-22%. Overall, the event rate in patients with two normal tests at one year was three-fold lower than in patients with one abnormal test and six-fold lower than in patients with both tests abnormal. In a time-dependent analysis of hazard ratios, EPS was a significant predictor of events starting at nine months and continuing throughout the rest of the study. In contrast, MTWA was predictive in the early phase of follow-up but no longer predictive by 12 to 24 months.
Costantini et al concluded that a strategy involving MTWA and EPS might be used to identify low-risk patients who meet other criteria for ICD implant for primary prevention of sudden cardiac death.
The utility of MTWA as an effective risk stratifier for patients who are potential candidates for ICD implants remains controversial. Some studies have shown that MTWA can be used to identify low-risk patients, but in other recent studies, such as the MASTER trial (J Am Coll Cardiol. 2008;52:607-615) or the Sudden Cardiac Death Heart Failure Trial (Circulation. 2008;118:2022-2228), the predictive value of MWTA tests was less apparent. In patients with left ventricular systolic dysfunction, current pharmacologic therapy has resulted in most primary prevention groups being "low risk." Exactly how low the annual risk should be in order to justify ICD implants remains uncertain. The early primary prevention studies had two- or three-year event rates that ranged between 20% and 40%. However, more recent studies, including the ABCD trial reported here, have shown much lower early event rates, and a negative test result is less important.
A large fraction of the costs and risks associated with ICD therapy occur at, or early after, implant. The average longevity of the most costly component, the ICD generator itself, should be at least five years. Therefore, studies that assess the value of risk stratification should probably use a longer follow-up duration than the 1-2 years seen in this study. Perhaps, future data from the ABCD investigators will provide further insights into the value of MTWA testing.