BackgroundThrombolytic therapy reduces mortality after acute myocardial infarction, even when treatment is initiated relatively late after onset of symptoms. The mechanism underlying this survival benefit is incompletely understood.Methods and ResultsIn a prospectively designed ancillary study of a randomized, placebo-controlled trial of late thrombolytic therapy (LATE), the signal-averaged (SA) ECG was recorded before hospital discharge in an effort to assess the effect of thrombolytic therapy on arrhythmia substrate. Three hundred ten patients were enrolled at 23 participating sites; 160 patients received placebo, and 150 patients received recombinant tissue-type plasminogen activator (rTPA) therapy 6 to 24 hours after onset of symptoms. Compared with placebo, rTPA tended to reduce the frequency of SAECG abnormality (filtered QRS duration >120 milliseconds) by 37% (95% CI, −64%, +6%;P=.087) and the filtered QRS duration (105.7±13.8 versus 108.8±14.6 milliseconds,P=.05). In the prespecified subgroup of 185 patients with ST elevation on the qualifying ECG, rTPA resulted in a 52% reduction (95% CI, 4% to 77%,P=.011) of SAECG abnormality and a shorter filtered QRS duration (105.7±10.9 versus 110.7±15.9 milliseconds,P=.01). No benefit was seen in patients without ST elevation on ECG.ConclusionsLate thrombolytic therapy produced a more stable electrical substrate, which probably represents an important mechanism of mortality benefit.