European Heart Journal Advance Access originally published online on July 17, 2006
European Heart Journal 2006 27(17):2040-2045; doi:10.1093/eurheartj/ehl149
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Angiographically evident thrombus following fibrinolytic therapy is associated with impaired myocardial perfusion in STEMI: a CLARITY-TIMI 28 substudy
1 Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
2 Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA
Received 16 May 2006; revised 14 June 2006; accepted 22 June 2006; online publish-ahead-of-print 17 July 2006.
* Corresponding author: 350 Longwood Avenue, First Floor, Boston, MA 02115, USA. Tel: +1 617 278 0145; fax: +1 888 249 5261. E-mail address: mgibson{at}timi.org
Aims The presence of residual thrombus following fibrinolytic therapy for ST-segment elevation myocardial infarction (STEMI) may predispose to greater embolization and microvascular dysfunction.
Methods and results We hypothesized that even in the presence of a patent epicardial artery, residual thrombus would be associated with worsened TIMI myocardial perfusion grades (TMPG), independent of epicardial flow. Data were analysed from the angiograms of 2684 patients enrolled in the CLARITY-TIMI 28 trial, with angiographically patent arteries (TIMI 2/3 flow) at a median of 88 h following fibrinolytic therapy. Thrombus in a patent epicardial artery was observed more frequently among patients with shorter times from randomization to angiography, among patients with non-left anterior descending infarctions, and among patients treated with placebo (vs. clopidogrel). Thrombus was associated with more frequent TIMI 2 flow (35.1 vs. 22.1%, P<0.001), higher corrected TIMI frame counts (CTFC) (42 vs. 33 frames, P<0.001), and a lower incidence of normal TMPG 3 (48.7 vs. 63.9%, P<0.001), irrespective of treatment with clopidogrel or placebo. In multivariable analyses, thrombus remained associated with higher CTFC (P<0.001) and worse TMPG (OR 1.6 for TMPG 0/1/2, P<0.001) after adjustment for baseline covariates as well as known correlates of TMPG. The association between thrombus and impaired TMPG remained even after further adjustment for CTFC or TIMI flow grade.
Conclusion Residual angiographic thrombus following fibrinolytic therapy in STEMI patients is associated with impaired myocardial perfusion, independent of epicardial flow. This finding emphasizes the roles of platelet aggregation and distal embolization in the pathogenesis of microvascular dysfunction in STEMI.
Key Words: Thrombus • TIMI myocardial perfusion grade • Corrected TIMI frame count • TIMI flow grade • ST-elevation myocardial infarction