Latent microvolt T-wave alternans in survivors of unexplained cardiac arrest unmasked by epinephrine challenge

Heart Rhythm. 2012 Jul;9(7):1076-82. doi: 10.1016/j.hrthm.2012.02.026. Epub 2012 Feb 25.


Background: The arrhythmogenic substrate in survivors of unexplained cardiac arrest (UCA) has not been defined.

Objectives: To test the hypothesis that patients with UCA have latent repolarization abnormalities, in particular T-wave alternans (TWA), which may be unmasked with epinephrine (EPI) challenge.

Methods: We prospectively studied 10 UCA survivors (46 ± 9 years) and 11 first-degree relatives (FDRs) of sudden death victims (37 ± 14 years). Patients with UCA underwent standard clinical testing, which was normal. FDRs had normal clinical history and testing. All subjects underwent an EPI infusion (0.05, 0.1, and 0.2 μg/(kg·min), 5 minutes each dose) while recording continuous digital 12-lead electrocardiograms. Corrected QT interval and QT variability index were evaluated at each EPI dose. TWA magnitude (V(alt)) was assessed at each dose by using the spectral method. Positive (+) TWA at each dose was defined as V(alt) > 0 with k ≥ 3 in 1 or more 128-beat segment in ≥2 electrocardiogram leads. A novel metric, TWA burden, reflecting V(alt) integrated over time (s), was also evaluated for each EPI dose.

Results: There was no difference between UCA survivors and FDRs with respect to heart rate, QT, corrected QT interval, or QT variability index at baseline or during EPI. At baseline, +TWA was similar between UCA survivors and FDRs (10% vs 0%; P = NS). During EPI, +TWA was more prevalent in UCA survivors than in FDRs (80% vs 18%; P = .009). TWA burden was greater in UCA survivors than in FDRs during EPI 0.1 (P = .039) and EPI 0.2 μg/(kg·min) (P = .009).

Conclusions: UCA survivors are more likely to demonstrate latent TWA compared with FDRs, which becomes manifest with EPI. This novel finding provides evidence for an arrhythmogenic substrate in UCA survivors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / administration & dosage
  • Death, Sudden, Cardiac
  • Dose-Response Relationship, Drug
  • Electrophysiologic Techniques, Cardiac
  • Epinephrine / administration & dosage
  • Heart Arrest / physiopathology*
  • Heart Conduction System / physiopathology*
  • Humans


  • Adrenergic beta-Agonists
  • Epinephrine