Faculty Bibliography

In the Second Mt. Sinai-New York University Reperfusion Trial, in which change of ejection fraction was the primary end point, the following secondary end points were prospectively assessed by serial coronary angiography: patency of the infarct artery both before intervention and 10-14 days later, acute and delayed recanalization rates, presence or absence of collateral flow, and complication rates of acute interventional catheterization. We assigned 393 patients randomly to groups receiving acute cardiac catheterization and a double-blind intracoronary infusion of streptokinase (SK arm), both streptokinase and nitroglycerin (SK-NTG arm), nitroglycerin alone (NTG arm), or conventional therapy without acute catheterization (control arm). Prospective stratification was based on duration of infarct pain before randomization: group A, less than 2 hours; Group B, 2-12 hours. Baseline patency rates were comparable in patients studied within 6 hours (30%, 40 of 135) and those studied later (24%, 32 of 133). This finding refutes the hypothesis that spontaneous recanalization occurs frequently after 6 hours. The acute recanalization rates of the SK arm (60%, 40 of 67) and the SK-NTG arm (63%, 29 of 62) did not differ. During streptokinase infusion, more vessels recanalized in group A (81%, 22 of 27) than in group B (56%, 57 of 102) (p less than 0.01); this was due to a significant reduction of recanalization rates from 75% (48 of 64) to 45% (26 of 62) with treatment after 6 hours (p less than 0.01). Delayed recanalization, that is, patency at end point but not postintervention, was seen in 17% (17 of 100) of total occlusions treated with streptokinase. In group A, all total occlusions treated with streptokinase recanalized either acutely (20 of 22) or delayed (two of 22), whereas in group B, 23% (18 of 78) remained obstructed. The reocclusion rate in the SK arms was 17% (11 of 65). In the NTG arm, recanalization occurred during intervention in 4% (two of 47) and delayed in 45% (21 of 47). At end-point angiography, the patency rates of the NTG arm (62%, 41 of 66) and the control arm (58%, 36 of 62) were comparable; those of the SK arms were higher (75%, 105 of 140) (p less than 0.01). Total occlusion was associated with collateral flow in 33% (66 of 199) at baseline; the prevalence of collaterals did not increase with time to angiography, which indicates that they had developed before the index event.(ABSTRACT TRUNCATED AT 400 WORDS)

The change in left ventricular ejection fraction from preintervention to predischarge was prospectively assessed in 393 patients with acute myocardial infarction. Within 12 h of symptom onset (mean 6.3 +/- 2.7 h), patients were randomly assigned to a double-blind intracoronary infusion of streptokinase, nitroglycerin, both streptokinase and nitroglycerin or conventional therapy without acute cardiac catheterization. Treatment effects were also assessed in prospectively defined angiographic subsets. There was a significant interaction between streptokinase and nitroglycerin (p less than 0.01), resulting in an increase in ejection fraction of 3.9 percentage units in the combined treatment arm (p less than 0.001). Patients with collateral flow to a totally obstructed infarct-related artery showed a significant improvement over those without collateral flow in the streptokinase (5.4 +/- 2.5%) and streptokinase-nitroglycerin (10.6 +/- 2.7%) arms, but not in the nitroglycerin arm. Time to treatment did not influence the change in ejection fraction. In patients with initial subtotal occlusion, thrombolytic therapy was of no short-term benefit because ejection fraction increased by 6% in all three intervention arms. These findings indicate that relatively late thrombolytic therapy results in significant myocardial salvage in those patients with collateralized total coronary occlusion. This benefit is potentiated by concomitant nitroglycerin therapy

Two indexes of collateral blood flow, the ratio of distal coronary occlusion pressure/aortic pressure (DCOP/Pao) and angiographic collateral class were determined during elective angioplasty in 36 patients with normal left ventricular function. The association between collateral indexes and 8 anatomic and clinical variables was assessed. A reduction in luminal diameter by greater than or equal to 70% predicted angiographically demonstrable collaterals with 100% specificity and 85% sensitivity. Lesion severity (stenosis) correlated with both collateral class and DCOP/Pao: DCOP/Pao = 2.8809 - 0.0729 X stenosis + 0.00049 X stenosis. The data suggest a quantitative relation between lesion severity and collateral development beyond a threshold value of 70% stenosis. Left ventricular ejection fraction during ischemia caused by balloon occlusion (EFo) was found to be primarily determined by lesion location; however, collateral flow modified EFo significantly. For mid-left anterior descending and right coronary artery: EFo = 59 + 26 X (DCOP/Pao); for proximal left anterior descending artery: EFo = 24 + 89 X (DCOP/Pao). A model predicting the hemodynamic and clinical consequences of abrupt coronary closure based on lesion location and severity was developed. In the second study phase, this model was tested retrospectively in a different group of 23 patients who experienced coronary occlusion as a complication of angioplasty. The data of both study phases suggest that left ventricular function and clinical outcome after abrupt coronary closure are determined by an interaction between location of the coronary artery obstruction and the amount of collateral flow. Lesion severity and the extent of functional impairment resulting from abrupt coronary closure are inversely related

We randomly assigned patients with a clinical diagnosis of acute myocardial infarction to one of four treatment groups: intracoronary streptokinase, intracoronary nitroglycerin, intracoronary streptokinase and intracoronary nitroglycerin, or conventional therapy without initial angiography. Of 124 patients 122 sustained acute myocardial infarction. Initial angiography revealed total occlusion of the coronary artery responsible for infarction in 67 per cent (61 of 91). Acute recanalization occurred in 74 per cent (32 of 43) of patients receiving streptokinase but in only 6 per cent (1 of 18) of patients treated with nitroglycerin alone (P less than 0.01). At angiography of all four groups on Day 10 to 14 the vessel responsible for acute myocardial infarction was patent in 77 per cent (71 of 92) of patients; there was no difference among groups, indicating gradual, endogenous thrombolysis in patients not treated with streptokinase. Patients with subtotal obstruction initially had significant improvement in left ventricular function, significantly lower peak creatine kinase levels, and a trend toward lower mortality than patients with total occlusion initially. Mortality at six months in patients receiving streptokinase (21 per cent, 13 of 62) did not differ significantly from that in patients not treated with streptokinase (10 per cent, 6 of 61). Additional studies will be necessary to assess treatment effects in the angiographic subsets identified by this trial