Noninvasive sudden death risk stratification by ambulatory ECG-based T-wave alternans analysis: evidence and methodological guidelines

Abstract

Extensive experimental and clinical evidence supports the utility of T-wave alternans (TWA) as a marker of risk for ventricular fibrillation. This entity appears to reflect the fundamental arrhythmogenic property of enhanced dispersion of repolarization. This relationship probably accounts for its relative ubiquity in patients with diverse types of cardiac disease, as has been recognized with the development of analytical tools. A basic premise of this review is that ambulatory ECG monitoring of TWA as patients experience the provocative stimuli of daily activities can expose latent electrical instability in individuals at heightened risk for arrhythmias. We will discuss the literature that supports this concept and summarize the current state of knowledge regarding the use of routine ambulatory ECGs to evaluate TWA for arrhythmia risk stratification. The dynamic, nonspectral modified moving average analysis method for assessing TWA, which is compatible with ambulatory ECG monitoring, is described along with methodological guidelines for its implementation. Finally, the rationale for combined monitoring of autonomic markers along with TWA will be presented.

Figure 1

Examples of significant T‐wave alternans during ischemic events in three representative patients from the ASIS trial. The ECGs were obtained from the V₅ leads. (Reproduced with permission from Futura from Ref. 47.)

Figure 2

Flow chart of the major components of the MMA method illustrated with AECG data from a post‐MI patient enrolled in the ATRAMI study who had an arrhythmic event during follow‐up. The odd ECG beats in the sequence are assigned to Group A and the even ECG beats to Group B. MMA computed beats of types A and B are updated continuously. The alternans estimate is determined as the maximum absolute difference between A and B computed beats within the ST segment and T‐wave region. (Reproduced with permission from Blackwell Publishing from Ref. 50.)

Figure 3

Magnitude of TWA response in cases and controls in leads V₁ and V₅ from the ATRAMI study. At baseline, the values were similar for cases and controls, as indicated by the P values. At each of the three predetermined study points of maximum heart rate, 8:00 am, and maximum ST‐segment deviation, TWA was significantly elevated over baseline in both cases and controls (P <<0.01). The rise in TWA at maximum heart rate and at 8:00 am was significantly greater in cases than controls in lead V₅. (Reproduced with permission from Blackwell Publishing from Ref. 50.)

Figure 4

Comparison of ICD patients with controls in T‐wave alternans responses to mental stress and exercise (Δ= change from baseline). Increases in TWA were higher in ICD patients than in controls during mental arithmetic (P = 0.043), exercise stage 1 (P = 0.0004), and peak exercise (P = 0.038). *P <0.05, **P <0.01 (ICD vs control). (Adapted with permission from Lippincott, Williams & Wilkins from Ref. 26.)