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

Abstract

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.

Postictal increase in T-wave alternans after generalized tonic-clonic seizures

“…TWA following sGTCS seems to be an independent marker, as it did not correlate with HR and returned to baseline after 15 min, in contrast to the impaired HR recovery, which lasted for at least 30 min after seizure cessation. Experimental studies have demonstrated that HR is only one determinant of TWA, as autonomic neurotransmitters and changes in myocardial substrate can provoke elevated levels of TWA during fixed rate pacing (Nieminen & Verrier, 2010). Furthermore, TWA was not different at both baselines at 4:00 a.m. and 8:00 a.m. as compared to otherwise healthy patients with NREM parasomnia.…”

“…Impaired cardiac recovery as assessed by persistent elevations of HR after exercise or decreased HRV are long‐established electrocardiographic predictors of arrhythmic death (McLaughlin & Zimetbaum, 2006). During the past decade T‐wave alternans (TWA) has been identified as a novel independent predictor of risk of sudden cardiac death and cardiovascular mortality (Hering, 1909; Rosenbaum et al., 1994; Nieminen & Verrier, 2010). TWA is a beat‐to‐beat alternation in morphology and amplitude of the ST segment or T wave that reflects temporal‐spatial heterogeneity of repolarization (Nearing & Verrier, 2003).…”

Late gadolinium enhancement of cardiac magnetic resonance imaging indicates abnormalities of time-domain T-wave alternans in hypertrophic cardiomyopathy with ventricular tachycardia

“…This method has been described in detail in the original report. 11,19 Briefly, the modified moving average algorithm continuously streams odd and even beats into separate bins and creates median complexes at any point within the JT segment and it is regarded as the TWA value, which is updated every 15 seconds. The moving average algorithm allows control of the influence of new incoming beats on the median complexes with an adjustable update factor, which was 1/8 in this analysis.…”

Detection and evaluation of ventricular repolarization alternans: An approach to combined ECG, thoracic impedance, and beat-to-beat heart rate variability analysis

“…Experimental [2,3] and clinical [4] studies indicate that TWA appears in cases of temporal-spatial heterogeneity of ventricular repolarization, which is a critical factor in arrhythmogenesis arising in different cardiac pathologies. The phenomena can establish the preconditions for conduction block, reentry, and life-threatening arrhythmias what may cause sudden cardiac death [5,6].…”