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ACUTE MYOCARDIAL ISCHEMIA/INFARCTION

Association of duration of symptoms at presentation with angiographic and clinical outcomes after fibrinolytic therapy in patients with st-segment elevation myocardial infarction

C. Michael Gibson, MS, MD^*,*, Sabina A. Murphy, MPH^*, Ajay J. Kirtane, MD^*,, Robert P. Giugliano, MD, SM^*, Christopher P. Cannon, MD^*, Elliott M. Antman, MD^*, Eugene Braunwald, MD^* TIMI Study Group

^* TIMI Study Group, Cardiovascular Division, Brigham & Women's Hospital
Cardiovascular Division, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MassachusettsUSA

Manuscript received March 12, 2004; revised manuscript received May 6, 2004, accepted May 11, 2004.

^* Reprint requests and correspondence: Dr. C. Michael Gibson, 350 Longwood Avenue, First Floor, Boston, Massachusetts 02115 (Email: mgibson{at}timi.org).

OBJECTIVES: 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 ratio1.14 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.

Abbreviations and Acronyms   CHF = congestive heart failure   CTFC = corrected Thrombolysis In Myocardial Infarction frame count   LAD = left anterior descending   PCI = percutaneous coronary intervention   OR = odds ratio   rt-PA = recombinant tissue-type plasminogen activator   STEMI = ST-segment elevation myocardial infarction   TFG = Thrombolysis In Myocardial Infarction flow grade   TIMI = Thrombolysis In Myocardial Infarction   TMPG = Thrombolysis In Myocardial Infarction myocardial perfusion grade   TNK = tenecteplase   t-PA = tissue-type plasminogen activator

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