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

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.