Elsevier

Journal of Electrocardiology

Volume 46, Issue 6, November–December 2013, Pages 585-590
Journal of Electrocardiology

Clinical applications of T-wave alternans assessed during exercise stress testing and ambulatory ECG monitoring☆,☆☆,★

https://doi.org/10.1016/j.jelectrocard.2013.06.006Get rights and content

Abstract

Analytical methods to measure T-wave alternans (TWA), a beat-to-beat fluctuation in the morphology of the ST-segment and T wave in the electrocardiogram (ECG), have been developed to address the unmet challenge of identifying individuals at increased risk for sudden cardiac death. Conventional noninvasive markers including left ventricular ejection fraction have significant limitations as many individuals who die suddenly have relatively preserved ventricular mechanical function. TWA is an attractive marker as it is closely linked to ECG heterogeneity and abnormalities in calcium handling, key factors in arrhythmogenesis. The objectives of this review are to summarize the clinical evidence supporting use of TWA in risk stratification and to discuss its current and potential applications in guiding device and medical therapy.

Introduction

Identification of individuals at risk for sudden cardiac death (SCD), which claims ~ 310,000 lives in the U.S. alone annually,1 remains an elusive challenge in cardiology. The urgency of this problem is underscored by the fact that in 30% of cases, premature death is the first manifestation of latent disease. Conventional markers have not proved sufficiently reliable. The primary noninvasive indicator of cardiovascular risk, left ventricular ejection fraction (LVEF), has significant limitations, as many individuals who succumb to SCD have relatively preserved cardiac mechanical function and conversely, a substantial proportion of patients with compromised LVEF do not die suddenly.

T-wave alternans (TWA) is characterized by a beat-to-beat fluctuation in ST-segment or T-wave morphology (Fig. 1).2 This phenomenon has emerged as a useful marker of risk for cardiovascular mortality and SCD. The link between TWA and risk for SCD rests on sound scientific underpinnings as it has been shown to be correlated with heterogeneity of repolarization and abnormalities in intracellular calcium handling, major factors in arrhythmogenesis, as discussed elsewhere in this issue.3 Rapid heart rates can challenge the capacity for intracellular calcium cycling and TWA can occur in normal individuals at elevated rates. For this reason, TWA tests generally incorporate an upper limit, typically 125 beats/min.

Section snippets

Methods for TWA assessment

Two main techniques have been used to measure microvolt levels of TWA in clinical studies, the Spectral and Modified Moving Average (MMA) Methods.

The Spectral Method employs Fast Fourier Transform to calculate the amplitude of the spectrum at 0.5 cycle/beat.4 It requires raising and fixing heart rate at 105–110 beats per minute (bpm) and records the ECG with specialized electrodes. The principles of analysis are illustrated in Fig. 2A.5 TWA levels ≥ 1.9 μV with alternans signal-to-noise ratio K > 

Exercise-based TWA analysis

A basic tenet of TWA testing is that its capacity to uncover latent electrical instability is optimized by subjecting the heart to a standardized physiologic challenge. Exercise has been used as the main stimulus incorporating the important elements of increased heart rate, enhanced sympathetic nerve activity, and elevated cardiac metabolic demand. Exercise stress testing has been employed with both the Spectral and MMA Methods.

Support for the utility of TWA testing with the Spectral Method is

Guiding ICD implantation

Identification of patients who would not benefit from ICD implantation, particularly those fulfilling Multicenter Automatic Defibrillator Trial II (MADIT II) indications, namely, prior myocardial infarction and LVEF < 30%, has been the main focus of TWA studies with the spectral method.17 The implantable cardioverter defibrillator (ICD) interventional trials using the Spectral Method, including the Microvolt T-Wave Alternans Testing for Risk Stratification of Post-Myocardial Infarction Patients

Quantitative analysis of TWA voltage for expanding clinical applications

Because TWA reflects a continuum of cardiac electrical instability, its quantification can enhance the potential for diagnosing levels of risk and for improving prognostic capacity, as treating a continuous variable as binary decreases predictive power by 33–50%. Clinical studies employing either the Spectral24 or MMA methods25 demonstrate that higher TWA magnitudes indicate greater risk for ventricular tachyarrhythmias. In patients with infarct-related or nonischemic cardiomyopathy, TWA

Conclusions

A sizeable body of evidence from prospective studies in > 12,000 patients with depressed or preserved LVEF supports the utility of TWA analysis in evaluating risk for cardiovascular mortality and sudden cardiac death.2 Multivariate analyses confirm that TWA provides information on risk beyond standard clinical variables for cardiovascular disease, including demographic factors (e.g., age, sex, and race) and contemporary cardiovascular risk markers (e.g., smoking, blood pressure, history, and

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    Disclosures: RLV receives post-market royalties from Georgetown University and Beth Israel Deaconess Medical Center for the Modified Moving Average algorithm for TWA measurement, which is licensed to GE Healthcare.

    ☆☆

    MM declares no conflicts of interest.

    ★

    No funding was received for preparation of this review.

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