Relationship between therapeutic time intervals and intermediate term left ventricular systolic function in patients...

The concept of initiating fibrinolytic therapy in patients who cannot undergo immediate percutaneous coronary intervention (PCI) in the setting of acute ST-segment-elevation myocardial infarction (STEMI) has been proposed as a strategy to improve outcomes. However, evidence supporting the use of this strategy is not conclusive, and the results of recent randomized controlled trials are apparently contradictory. Probably, the time points of administration of the adjunctive thrombolytics and antiplatelet agents and the time loss until coronary intervention have a major influence on the discrepancy of outcomes in different trials. Therefore, the relationship between therapeutic time intervals and outcome in patients treated with facilitated PCI has been analyzed.

In this single center retrospective study, 131 patients with STEMI were treated with a combined pharmaco-mechanical reperfusion strategy using half-dose r-tPA combined with a glycoprotein (GP) IIb/IIIa antagonist prior to PCI. Specific time points were recorded for each patient, including the time of symptom onset, the time of first medical contact, the start of intravenous thrombolysis, the time of administration of the GP IIb/IIIa antagonist and the start of coronary intervention. We then examined the relationship between the time delay from symptom onset to the initiation of various steps of treatment and the residual myocardial damage as expressed by the severity of both global and regional myocardial dysfunction calculated from a left ventriculography study performed 3 months later.

The median time from symptom onset to the first medical contact, with 25th and 75th percentiles in parentheses, was 1.25 h (0.75, 3), from symptom onset to initiation of thrombolytic therapy 2.25 h (1.25, 3), to initiation of GP IIb/ IIIa inhibitor therapy 3.5 h (2, 5.69), and to the start of coronary intervention 4.81 h (2.85, 7.91). The time between symptom onset and initiation of both thrombolytic therapy and coronary intervention was significantly related to the global ejection fraction and to the extent of regional hypokinesia at the 3-month follow-up (p<0.05). The time to the initiation of GP IIb/IIIa inhibitors was only significantly related to the global ejection fraction (p<0.05), while the time to the first medical contact did not show a similar relationship (p>0.05). Furthermore, we observed a significant relationship between the infarct-related artery (IRA) patency at the initial angiogram and the residual regional myocardial damage at follow-up; normokinesia at follow-up was found in 61.3% of patients with an initially patent IRA and in 41.2% of patients with an initially occluded IRA, whereas severe hypokinesia was found in 13.8% and 37.3%, respectively (p<0.05).

In patients with STEMI treated with a facilitated PCI strategy using half dose r-tPA in combination with a glycoprotein IIb/IIIa receptor blocker, the 3-month global and regional residual myocardial dysfunction is significantly related to the time elapsed between the onset of symptoms and the start of both fibrinolytic therapy and coronary intervention.