Quality of Reperfusion

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Besides early administration of therapy, complete reperfusion, or Thrombolysis in MI (TIMI) 3 flow in the infarct artery at 90 min is also an extremely potent predictor of improved outcome. The primacy of rapid and sustained infarct artery patency was highlighted in the angiographic substudy of the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO) I trial (14). As compared with lesser degrees of reperfusion, TIMI 3 flow was associated with a markedly improved survival at 30 d (Fig. 4). Simes et al. (15) showed that the differences in the rate of TIMI 3 flow at 90 min among the four fibrinolytic regimens tested in GUSTO I explained almost

Fig. 3. Reperfusion strategy and myocardial salvage index according to time to treatment. Adapted from ref. 13.

Fig. 3. Reperfusion strategy and myocardial salvage index according to time to treatment. Adapted from ref. 13.

entirely the differences in mortality among the four groups. Retrospective analyses of other fibrinolytic trials have confirmed this observation (16,17). Furthermore, even when brisk antegrade flow is initially achieved with lytic therapy, substantial attrition of the benefit occurs because of intermittent patency (25%), reocclusion (13%), and impaired microvasculature, or "no-reflow" (23%) (18). The concept of the "illusion of reperfusion" (19) reflects our overestimation of the actual rate of complete reperfusion induced by lytic therapy, which probably occurs in only a quarter of those treated.

Because, as compared with optimal fibrinolytic therapy, primary angioplasty is capable of achieving TIMI 3 flow in 15-35% more patients (14,20,21), it is reasonable to expect that this difference in patency rates will translate into clinical benefit. As a mechanistic confirmation of the improved outcome with better patency, the relation between completeness of flow restoration with percutaneous transluminal coronary angioplasty (PTCA) and myocardial salvage was examined by Laster et al. in 180 patients enrolled in the Mayo Clinic Registry of Primary Angioplasty (22). TIMI 3 flow was achieved in 163 (91%) patients, TIMI 2 in 13 (7%) patients, and TIMI 0/1 in 4 (2%) patients of the group. Postangioplasty TIMI flow grade was significantly associated with infarct size and degree of myocardial salvage. In a pooled analysis of the four Primary Angioplasty in Myocardial Infarction (PAMI) trials, Stone et al. showed in nearly 2300 patients that TIMI 3 flow after angioplasty is associated with a 6-mo mortality of only 2.6%, while patients with lesser reperfusion had substantially higher mortality (6.1% for TIMI 2 and 22.2% for TIMI 0/1 flow, p < 0.0001) (23). Furthermore, preangioplasty flow had a significant impact on the ability to achieve TIMI 3 flow after angioplasty (91.5% if TIMI < 3 flow before intervention vs 98.1% if TIMI 3 flow was present), as well as on 6-mo mortality (Fig. 5). As described later in the chapter, this observation becomes important as strategies to facilitate primary angioplasty are developed.

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