Methodologic drift in the assessment of TIMI grade 3 flow and its implications with respect to the reporting of angiographic trial results. The TIMI Study Group.

BACKGROUND: The Thrombolysis in Myocardial Infarction (TIMI) Study Group originally defined TIMI grade 3 flow (complete perfusion) as antegrade flow into the bed distal to the obstruction that occurs as promptly as antegrade flow into the bed proximal to the obstruction. Recently, several groups have defined TIMI grade 3 flow as opacification of the coronary artery within 3 cardiac cycles. METHODS AND RESULTS: On the basis of heart rate data at the time of the cardiac catheterization and the time for dye to go down the artery (TIMI frame count/30 = seconds), we estimated the number of patients who would meet the 3 cardiac cycle criterion and compared this with the number of patients with TIMI grade 3 flow by using the original definition in 1157 patients from 3 recent TIMI trials (10 A, 10B, and 14). In 74 patients without acute myocardial infarction and normal coronary arteries, the fraction of a cardiac cycle required for dye to traverse the artery was a mean of 0.93 +/- 0.34 cardiac cycles (n = 74) (median 0.80, minimum 0.44, maximum 2.1, none >3.0 cycles). The mean heart rate at 90 minutes after thrombolysis in the TIMI 14 trial was 79.6 +/- 16.8 beats/min (n = 194), and the duration of 3 cardiac cycles was a mean of 2.36 seconds, or a TIMI frame count of 70.8 frames. In all trials, the rate of TIMI grade 3 flow was 57.3% (n = 663/1157) with the original definition and 66.8% (n = 743/1113) with the <3 cardiac cycle definition (P <.001). CONCLUSIONS: A duration of 3 cardiac cycles for dye to traverse the artery lies approximately 6 SD above that observed in normal coronary arteries. A 3 cardiac cycle definition of TIMI grade 3 flow results in rates of normal perfusion that are approximately 10% higher than if the original definition of TIMI grade 3 flow is applied. Application of this simple correction factor may help place data reported with the 3 cardiac cycle definition of TIMI grade 3 flow in context.

Relationship between TIMI frame count and clinical outcomes after thrombolytic administration. Thrombolysis In Myocardial Infarction (TIMI) Study Group.

BACKGROUND: The corrected TIMI frame count (CTFC) is the number of cine frames required for dye to first reach standardized distal coronary landmarks, and it is an objective and quantitative index of coronary blood flow. METHODS AND RESULTS: The CTFC was measured in 1248 patients in the TIMI 4, 10A, and 10B trials, and its relationship to clinical outcomes was examined. Patients who died in the hospital had a higher CTFC (ie, slower flow) than survivors (69. 6+/-35.4 [n=53] versus 49.5+/-32.3 [n=1195]; P=0.0003). Likewise, patients who died by 30 to 42 days had higher CTFCs than survivors (66.2+/-36.4 [n=57] versus 49.9+/-32.1 [n=1059]; P=0.006). In a multivariate model that excluded TIMI flow grades, the 90-minute CTFC was an independent predictor of in-hospital mortality (OR=1.21 per 10-frame rise [95% CI, 1.1 to 1.3], an approximately 0.7% increase in absolute mortality for every 10-frame rise; P<0.001) even when other significant correlates of mortality (age, heart rate, anterior myocardial infarction, and female sex) were adjusted for in the model. The CTFC identified a subgroup of patients with TIMI grade 3 flow who were at a particularly low risk of adverse outcomes. The risk of in-hospital mortality increased in a stepwise fashion from 0.0% (n=41) in patients with a 90-minute CTFC that was faster than the 95% CI for normal flow (0 to 13 frames, hyperemia, TIMI grade 4 flow), to 2.7% (n=18 of 658 patients) in patients with a CTFC of 14 to 40 (a CTFC of 40 has previously been identified as the cutpoint for distinguishing TIMI grade 3 flow), to 6.4% (35/549) in patients with a CTFC >40 (P=0.003). Although the risk of death, recurrent myocardial infarction, shock, congestive heart failure, or left ventricular ejection fraction 20 to

Fatal cardiac rupture among patients treated with thrombolytic agents and adjunctive thrombin antagonists: observations from the Thrombolysis and Thrombin Inhibition in Myocardial Infarction 9 Study.

OBJECTIVES: The purpose of this study was to determine the incidence and demographic characteristics of patients experiencing cardiac rupture after thrombolytic and adjunctive anticoagulant therapy and to identify possible associations between the mechanism of thrombin inhibition (indirect, direct) and the intensity of systemic anticoagulation with its occurrence. BACKGROUND Cardiac rupture is responsible for nearly 15% of all in-hospital deaths among patients with myocardial infarction (MI) given thrombolytic agents. Little is known about specific patient- and treatment-related risk factors. METHODS Patients (n = 3,759) with MI participating in the Thrombolysis and Thrombin Inhibition in Myocardial Infarction 9A and B trials received intravenous thrombolytic therapy, aspirin and either heparin (5,000 U bolus, 1,000 to 1,300 U/h infusion) or hirudin (0.1 to 0.6 mg/kg bolus, 0.1 to 0.2 mg/kg/h infusion) for at least 96 h. A diagnosis of cardiac rupture was made clinically in patients with sudden electromechanical dissociation in the absence of preceding congestive heart failure, slowly progressive hemodynamic compromise or malignant ventricular arrhythmias. RESULTS A total of 65 rupture events (1.7%) were reported-all were fatal, and a majority occurred within 48 h of treatment Patients with cardiac rupture were older, of lower body weight and stature and more likely to be female than those without rupture (all p < 0.001). By multivariable analysis, age >70 years (odds ratio [OR] 3.77; 95% confidence interval [CI] 2.06, 6.91), female gender (OR 2.87; 95% CI 1.44, 5.73) and prior angina (OR 1.82; 95% CI 1.05, 3.16) were independently associated with cardiac rupture. Independent predictors of nonrupture death included age >70 years (OR 3.68; 95% CI 2.53, 5.35) and prior MI (OR 2.14; 95%, CI 1.45, 3.17). There was no association between the type of thrombin inhibition, the intensity of anticoagulation and cardiac rapture. CONCLUSIONS Cardiac rupture following thrombolytic therapy tends to occur in older patients and may explain the disproportionately high mortality rate among women in prior dinical trials. Unlike major hemorrhagic complications, there is no evidence that the intensity of anticoagulation associated with heparin or hirudin administration influences the occurrence of rupture.

Relation between injections before 90-minute angiography and coronary patency: results of the thrombolysis in myocardial infarction 4 trial.

The current goal of thrombolytic therapy is to achieve both full (Thrombolysis in Myocardial Infarction [TIMI] grade 3) and early reperfusion. Newer reperfusion strategies may now achieve a high degree of reperfusion even earlier than the traditional 90-minute end point. To determine whether injections before 90 minutes affect this traditional end point, the relation between the number of injections before 90-minute angiography and patency was examined in the TIMI 4 trial. The number of injections before 90-minute angiography was no different between occluded arteries (TIMI grade 0/1 flow) (2.46 +/- 1.78; n = 94) and patent arteries (TIMI grade 2/3 flow) (2.71 +/- 2.42; n = 295) (p = 0.24). The incidence of any injections before 90 minutes was no different in patent versus closed arteries (80.6% [77/98] vs 72.4% [22/304]; p = 0.10). The number of injections before 90 minutes was insignificantly smaller in patients with TIMI grade 3 flow (2.53 +/- 2.53 [n = 184] vs 2.76 +/- 2.03 [n = 204]; p = 0.31), but the incidence of any injections before 90 minutes was significantly smaller in patients with TIMI grade 3 flow (68.8% [132/192] vs 79.5% [167/210]; p = 0.01). No relation was identified between the number of injections before 90-minute angiography and patency at this traditional time point. This observation justifies the judicious use of a limited number of "earlier snapshots" of the infarct-related artery before 90 minutes to ascertain just how rapidly newer thrombolytic regimens achieve patency. Patients with TIMI grade 3 flow had a slightly lower incidence of injections before 90 minutes, perhaps because they did not require as urgent a definition of coronary anatomy.

Bowel and mesenteric injury following blunt abdominal trauma: evaluation with CT.

Computed tomography (CT) used in cases of blunt abdominal trauma has been found sensitive in detection of bowel and mesenteric injuries and discrimination of operable from nonoperable candidates. In 51 patients with suspected bowel or mesenteric injury following blunt abdominal trauma, CT correctly depicted bowel hematoma or mesenteric injury in 17 of 19 nonoperable patients (89%) and severe injuries in one patient who died preoperatively. In 26 of 28 patients who underwent therapeutic laparotomy (93%), initial CT enabled identification of surgically confirmed injuries. In two cases, initial scan misinterpretation delayed diagnosis of serious bowel injuries. The correct interpretation was rendered preoperatively and at blind retrospective review. CT findings that correlated with bowel or mesenteric injury requiring surgery were free peritoneal fluid (27 of 28, 96%), mesenteric infiltration (24 of 28, 86%), thick-walled bowel (17 of 28, 61%), associated abdominal injuries (12 of 28, 43%), and free air (nine of 28, 32%). In nonoperable cases, CT scans demonstrated bowel thickening (84%) but less frequently peritoneal fluid (21%), mesenteric infiltration (26%), or associated injuries (5%). In three of four patients who underwent nontherapeutic laparotomy, preoperative CT correctly imaged the limited abdominal injuries.