Clinical use of microvolt T-wave alternans in patients with depressed left ventricular function eligible for ICD implantation: mortality outcomes after long term follow-up

Implantable cardioverter-defibrillators (ICDs) reduce mortality in patients with left ventricular dysfunction. However, left ventricular dysfunction alone has significant limitations as a risk stratifier for guiding ICD therapy [1,2]. In the SCD-HeFT trial [3], the ICDmediated reduction in absolute mortality was 1.4% per year (7.2% over 5 years) indicating that only a very small fraction of patients with ICDs actually receive life saving therapy from the devices. Moreover, ICD implantation [4] is associated with a high rate of subsequent complications suchas infections, inappropriate shocks, leadand generator failures and recalls. Consequently there is a need to more accurately identify those individuals who will benefit from ICD implantation. Microvolt T-wave alternans (MTWA) has been linked mechanistically to the development of ventricular tachyarrhythmias [5] and is a clinical marker of increased risk of sudden cardiac death (SCD) [6–8]. Conversely, patients with a negative MTWA test have a very low risk of SCD [8]. In our departmentwe routinely measureMTWA in patients without a history of cardiac arrest being considered for prophylactic ICD implantation [9] and the result is a major determinant of the decision of whether or not to implant an ICD. From 2001 to March 2011 MTWA tests were performed on 178 consecutive patients with ischemic and non-ischemic cardiomyopathy who were eligible for ICD implantation according to clinical guidelines in place at the time of evaluation. Patientswith a normal testwere offered the option to not receive an ICD. We conducted long-term follow-up of these patients. The primary endpointwas defined as all-causemortality and the secondary endpoint was defined as cardiac mortality. Patients underwent an MTWA exercise bicycle testing that was interpreted both automatically within the HearTwave system and by two expert readers. Because patients with positive and indeterminate MTWA tests results display elevated event rates [8], all comparisons in this analysis were made between patients with normal (negative) and abnormal (positive or indeterminate) MTWA tests. The baseline characteristics of the 178 patients are listed in Table 1. All participantswere in NewYorkHeart Association functional class II or III and had left ventricular ejection fraction ≤ 40% (mean 30 ± 6). The MTWAabnormal patients compared to theMTWAnormal patients, on a statistically univariate basis, had higher NYHA class, wider QRS, and lower LVEF.MTWAwasabnormal in129 (72%)andnormal in49patients (28%). Substantially fewer patients (15/49, 31%) in the MTWA normal group received an ICD than did patients in the MTWA abnormal group (103/129, 80%), p = 0.0001. During the follow-up (median 64 months) a total of 35 deaths occurred. In the MTWA normal group 4 patients died – all of noncardiac cause; in the MTWA abnormal group 31 deaths occurred and were classified as follows: 20 cardiac deaths, 7 non-cardiac and 4 unknown.