Usefulness of T-Wave Alternans in Sudden Death Risk Stratification and Guiding Medical Therapy


  • Tuomo Nieminen M.D., Ph.D.,

    1. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
    2. Department of Pharmacological Sciences, Medical School, University of Tampere, Finland, and Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland
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  • Richard L. Verrier Ph.D.

    1. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
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  • Invited review for Revista Argentina de Cardiología and Annals of Noninvasive Electrocardiology.

  • Conflict of Interest: Dr. Verrier is co-inventor of the Modified Moving Average method for T-wave alternans analysis, with patent assigned to Beth Israel Deaconess Medical Center and licensed by GE Healthcare. Dr. Nieminen declares no conflicts of interest.

Address for correspondence: Richard L. Verrier, Ph.D., F.A.C.C., Harvard Medical School, Beth Israel Deaconess Medical Center, Harvard-Thorndike Electrophysiology Institute, 99 Brookline Avenue, RN-301, Boston MA 02215. Fax: 617-975-5270; E-mail:


Visible T-wave alternans (TWA), a beat-to-beat alternation in the morphology and amplitude of the ST segment or T wave, has been observed for over a century to occur in association with life-threatening arrhythmias in patients with acute coronary syndrome, heart failure, and cardiac channelopathies. This compelling linkage prompted development of quantitative techniques leading to FDA-cleared commercial methodologies for measuring nonvisible levels of TWA in the frequency and time domains. The first aim of this review is to summarize evidence from more than a hundred studies enrolling a total of >12,000 patients that support the predictivity of TWA for cardiovascular mortality and sudden cardiac death.

The second focus is on the usefulness of TWA in guiding therapy. Until recently, TWA has been used primarily in decision making for cardioverter-defibrillator implantation. Its potential utility in guiding pharmacologic therapy has been underappreciated. We review clinical literature supporting the usefulness of TWA as an index of antiarrhythmic effects and proarrhythmia for different drug classes. Beta-adrenergic and sodium channel-blocking agents are the most widely studied drugs in clinical TWA investigations, with both reducing TWA magnitude; the exception is patients in whom sodium channel blockade discloses the Brugada syndrome and provokes macroscopic TWA. An intriguing possibility is that TWA may help to detect beneficial effects of nonantiarrhythmic agents such as the angiotensin II receptor blocker valsartan, which indirectly protects from arrhythmia through improving myocardial remodeling. We conclude that quantitative analysis of TWA has considerable potential to guide pharmacologic intervention and thereby serve as a therapeutic target.

Ann Noninvasive Electrocardiol 2010;15(3):276–288