Association of duration of symptoms at presentation with angiographic and clinical outcomes after fibrinolytic therapy in patients with ST-segment elevation myocardial infarction.
OBJECTIVE
We sought to determine if an underlying mechanism of the association between prolonged symptom-to-treatment times and adverse outcomes may be an association of symptom-to-treatment times with impaired Thrombolysis In Myocardial Infarction myocardial perfusion grades (TMPGs).


BACKGROUND
Prolonged symptom duration among ST-segment elevation myocardial infarction (STEMI) patients undergoing fibrinolytic therapy is associated with adverse outcomes.


METHODS
Angiography was performed 60 min after fibrinolytic administration in 3,845 Thrombolysis In Myocardial Infarction (TIMI) trial patients.


RESULTS
The median time from symptom onset to treatment was longer among patients with impaired myocardial perfusion (3.0 h for TMPG 0/1 vs. 2.7 h for TMPG 2/3; p = 0.001). In a multivariate model, impaired tissue perfusion (TMPG 0/1) remained associated with increased time to treatment (odds ratio 1.14 per hour of delay; p = 0.007) even after adjusting for Thrombolysis In Myocardial Infarction flow grade (TFG) 3, left anterior descending infarct location, and baseline clinical characteristics. Impaired myocardial perfusion after rescue/adjunctive percutaneous coronary intervention (PCI) was associated with longer median times to treatment (3.0 h for TMPG 2/3 vs. 2.7 h for TMPG 0/1; p = 0.017), as was abnormal epicardial flow after rescue/adjunctive PCI (3.3 h for TFG 0/1/2 vs. 2.8 h for TFG 3; p = 0.005). Thirty-day mortality was associated with longer time from onset of symptoms to treatment (6.6% mortality for time to treatment >4 h vs. 3.3%; p < 0.001), even among patients undergoing rescue PCI.


CONCLUSIONS
A prolonged symptom to treatment time among STEMI patients is associated with impaired myocardial perfusion independent of epicardial flow both immediately after fibrinolytic administration and after rescue/adjunctive PCI. These data provide a pathophysiologic link between prolonged symptoms due to vessel occlusion, impaired myocardial perfusion, and poor clinical outcomes.
Gibson
C Michael
CM
TIMI Study Group, Cardiovascular Division, Brigham & Women's Hospital, Boston, Massachusetts, USA. mgibson@timi.org
Murphy
Sabina A
SA
Kirtane
Ajay J
AJ
Giugliano
Robert P
RP
Cannon
Christopher P
CP
Antman
Elliott M
EM
Braunwald
Eugene
E
D000368:Aged; D017023:Coronary Angiography; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D016032:Randomized Controlled Trials as Topic; D012039:Regional Blood Flow; D000077785:Tenecteplase; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase