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STATE-OF-THE-ART PAPER

Pathophysiological basis and clinical application of T-wave alternans

Antonis A. Armoundas, PhD^*,*, Gordon F. Tomaselli, MD^* and Hans D. Esperer, MD

^* Division of Molecular Cardiobiology, Johns Hopkins University, Baltimore, Maryland, USA
University Hospital, Division of Cardiology, Otto-von-Guericke University, Magdeburg, Germany

Manuscript received April 27, 2001; revised manuscript received March 20, 2002, accepted April 17, 2002.

^* Reprint requests and correspondence: Dr. Antonis A. Armoundas, Johns Hopkins University, Ross 844, 720 Rutland Avenue, Baltimore, Maryland 21205, USA.
antonis{at}pothos.bme.som.jhmi.edu

We review the contemporary understanding of the pathophysiology of repolarization alternans and present a perspective on the use of T-wave alternans (TWA) as a risk stratification marker of malignant ventricular arrhythmias. Several studies have demonstrated a high correlation of susceptibility to ventricular arrhythmias and sudden cardiac death with the existence of TWA. We describe a number of cellular and molecular alterations in the diseased heart that may provide a link between electrical and mechanical alternans and arrhythmia susceptibility. Repolarization alternans is likely the result of distinct and diverse cellular and molecular alterations that are associated with exaggerated regional repolarization heterogeneity, which renders the heart susceptible to malignant arrhythmias.

Abbreviations and Acronyms   AP   action potential   APD   action potential duration   DCM   dilated cardiomyopathy   ECG   electrocardiogram   EPS   electrophysiologic   FFT   fast Fourier Transform   HCM   hypertrophic cardiomyopathy   HRV   heart rate variability   ICD   implantable cardioverter-defibrillator   k   alternans ratio   LP   late potentials   LVEF   left ventricular ejection fraction   MI   myocardial infarction   MUSTT   Multicenter Unsustained Tachycardia Trial   NSVT   nonsustained ventricular tachycardia   RR   relative risk   SAECG   signal-averaged electrocardiography   SCD   sudden cardiac death   SR   sarcoplasmic reticulum   TWA   T-wave alternans   Valt   alternans magnitude   VF   ventricular fibrillation   VT   ventricular tachycardia

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