T‐Wave Alternans: Is It an Appropriate Test for Primary Prevention Implantable Cardioverter‐Defibrillator Risk Stratification?

Abstract

Abstract. Background. Several randomized controlled trials have demonstrated benefit for implantable cardio-verter-defibrillator (ICD) prophylaxis in selected patients. However, the absolute benefit of ICD prophylaxis on mortality is relatively small (5.6% or 7.2%) in patients selected using left ventricular ejection fraction (LVEF).1 Thus, only a few of the ICDs implanted prophylactically ever deliver appropriate therapy. The Center for Medicare & Medicaid Services (CMS) has accepted the scientific validity of these ICD prophylaxis trials, but has recognized the need for better risk stratification because the inconvenience, adverse effects, and cost of implanting ICDs in all patients who meet the criteria are substantial. Microvolt T-wave alternans (MTWA) testing can identify patients at increased risk of sudden cardiac death. The results of a study dealing with the use of MTWA in patients with either ischemic heart disease or nonischemic cardiomyopathy and LVEF ≤0.40 have recently been published. Methods. The study hypothesized that MTWA improves the selection of patients for ICD prophylaxis, especially by identifying patients who are not likely to benefit. The study was conducted at 11 clinical centers in the United States. Patients were eligible if they had an LVEF ≤0.40 and lacked a history of sustained ventricular arrhythmias; patients were excluded for atrial fibrillation, unstable coronary artery disease, or New York Heart Association (NYHA) functional class IV heart failure. Participants underwent an MTWA test and then were followed for approximately 2 years. The primary outcome was all-cause mortality or nonfatal sustained ventricular arrhythmias. Results. Ischemic heart disease was present in 49%, mean LVEF was 0.25, and 66% had an abnormal MTWA test. During 20±6 months of follow-up, 51 end points (40 deaths and 11 nonfatal sustained ventricular arrhythmias) occurred. Comparing patients with normal and abnormal MTWA tests, the hazard ratio for the primary end point was 6.5 at 2 years (95% confidence interval. 2.4–18.1; p<0.001). Survival of patients with normal MTWA tests was 97.5% at 2 years. The strong association between MTWA and the primary end point was similar in all subgroups tested. Conclusions. The authors concluded that 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.—Bloomfield DM, Bigger JT, Steinman RC, et al. Microvolt T-wave altemans and the risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction. J Am Coll Cardiol. 2006;47:456–463. Comment. The MTWA test, widely seen as a potential way to screen out patients who meet reimbursement criteria for primary-prevention ICD therapy, but probably won't ever need it, appeared to live up to that hope in this well designed study. MTWA is a simple test that monitors beat-to-beat microvolt-level variations in the shape of the electrocardiographic T wave during exercise stress. The MTWA is a simple, relatively inexpensive, noninvasive test that can be done routinely in a doctor's office using modifications of currently available exercise testing equipment. This study strongly suggests that MTWA testing can identify a large group of patients with left ventricular dysfunction who have an excellent prognosis and are unlikely to benefit from ICD prophylaxis. The investigators followed 549 patients with an LVEF ≤0.40 and no history of sustained ventricular arrhythmia, 66% of whom had tested positive for T-wave alternans. Most of the patients were in NYHA class II or III heart failure; the average LVEF was 0.25. Over a follow-up of up to 2 years, averaging 20 months, the one third of patients with normal baseline MTWA findings had a 2-year survival of 97.5%. The 11 instances of nonfatal sustained ventricular arrhythmias and 40 deaths were highly concentrated among those who had been MTWA-abnormal. Although LVEF wasn't predictive of such events in multivariate analysis, baseline MTWA emerged as a highly significant risk factor. As if to emphasize MTWA's potential risk-stratification advantage, the test identified a low-risk group among patients considered at especially high risk by conventional criteria. The 2-year event rate was 11.8% among those with an LVEF of 0.31–0.40 and an abnormal MTWA, but it was only 3.5% for an LVEF ≤0.30 with a normal MTWA. Based on MADIT-II2 and SCD-HeFT,3 according to the authors, about 18 or 14 ICDs, respectively, must be implanted to save one life. According to the current analysis, exclusion of lower-risk patients using the MTWA test would drop the number of implanted ICDs per life saved to seven. This improvement in numbers needed to treat to save one life can have a very substantial effect on the modern practice of cardiology, especially if one considers the economic factors. Will the medical community adopt this trial immediately, or wait while MTWA is being confirmed in other trials? Only time will tell.