Issues in the assessment of the safety and efficacy of tenecteplase (TNK-tPA).

While thrombolytic agents have demonstrated improved mortality over the use of placebo, this has come at the expense of bleeding complications such as intracranial hemorrhage (ICH). Tenecteplase (TNK-tPA) is a novel thrombolytic agent engineered to improve upon the ease of use and safety of alteplase (t-PA). Given its longer half-life, TNK-tPA can be administered as a single bolus. The dosing of TNK-tPA has been weight optimized to enhance both safety and efficacy outcomes. Weight-optimized TNK-tPA dosing requires body weight estimation, which may introduce the potential for medication error. However, data from TNK-tPA clinical trials suggest that body weight estimates can err by up to 20 kg (44 lb) without an increased risk of ICH or death. Furthermore, the results of TNK-tPA clinical trials showed that even at the highest weight-optimized dosage of 50 mg, ICH rates were among the lowest reported in clinical trials of thrombolytics for acute myocardial infarction. In elderly female patients of low body weight, the use of weight-optimized TNK-tPA lowered the risk of ICH compared with the use of t-PA, expanding the potential use of thrombolytics to this high-risk patient population. Tenecteplase has demonstrated clinical equivalence to t-PA, but with a wider therapeutic margin of safety.

Impact of contrast agent type (ionic versus nonionic) used for coronary angiography on angiographic, electrocardiographic, and clinical outcomes following thrombolytic administration in acute myocardial infarction.

The goal of this study was to examine the relationship between contrast agent type (ionic vs. nonionic) and angiographic, electrocardiographic, and clinical outcomes after thrombolytic administration. Ionic or nonionic contrast agents were selected in a nonrandomized fashion for 90-min angiography and percutaneous coronary intervention (PCI) following thrombolytic administration in the TIMI 14 trial [tissue plasminogen activator (tPA) or reteplase (rPA) vs. low-dose lytic + abciximab]. There was no relationship between contrast agent type and overall patency, rate of TIMI grade 3 flow, or corrected TIMI frame counts (CTFCs) in open culprit arteries and in post-PCI patency rates or post-PCI CTFCs. In patients treated with ionic contrast, ejection fractions at 90 min were slightly but significantly lower (56.2 +/- 16.5, n = 122, vs. 59.8 +/- 14.4, n = 322; P = 0.02), chest pain duration was longer (2.8 +/- 4.1 hr, n = 255, vs. 1.7 +/- 3.6, n = 550; P = 0.0003), and complete ST segment resolution was less frequent (41.5% vs. 50.8%; P = 0.04). While there was no difference in epicardial blood flow, ionic contrast agent use was associated with poorer ST segment resolution, longer chest pain duration, and poorer ejection fractions, perhaps as a result of microvascular dysfunction.

Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy.

BACKGROUND: Use of abciximab in combination with administration of thrombolytics has been shown to improve epicardial and microvascular coronary blood flow in acute myocardial infarction (AMI). As a potential mechanism, we hypothesized that combination therapy would reduce angiographically evident thrombus (AET) and would increase lumen diameter compared with thrombolytic monotherapy. METHODS AND RESULTS: Patients who received combination therapy in TIMI 14 (low-dose thrombolytic plus abciximab, n=732) were compared with patients who received thrombolytic monotherapy without abciximab in the TIMI 4, 10A, 10B, and 14 trials (n=1662). Thrombus burden was assessed 90 minutes after treatment, and quantitative angiography was performed in an angiographic core laboratory by investigators blinded to treatment assignment. The frequency of AET was reduced in patients who received abciximab combination therapy compared with thrombolytic monotherapy (26.6% versus 35.4%, P<0.001). Similar findings were observed when the analysis was restricted to patients with patent arteries (14.7% versus 20.8%, P=0.001). Residual percent diameter stenosis at 90 minutes was also improved in the abciximab therapy group both in patent arteries (64.6+/-16.6 versus 68.3+/-14.8, P<0.001) and between patent and occluded arteries (69.3+/-19.5 versus 73.8+/-17.9, P<0.001). The absence of AET was associated with an increased frequency of >70% ST-segment resolution by 90 minutes (37.2%, 110/296 versus 18.9%, 54/286, P<0.001). CONCLUSIONS: Compared with thrombolytic monotherapy, combination therapy with abciximab reduces AET, which in turn is associated with reduced residual stenosis and improved ST-segment resolution in AMI. These data provide a pathophysiological link between platelet inhibition, reduced thrombus, and improvements in both epicardial and microvascular perfusion in AMI.

Can we replace the 90-minute thrombolysis in myocardial infarction (TIMI) flow grades with those at 60 minutes as a primary end point in thrombolytic trials? TIMI Study Group.

The establishment of patency (Thrombolysis In Myocardial Infarction [TIMI] grade 2 or 3 flow) and/or TIMI grade 3 flow at 60 minutes after thrombolytic administration is both a univariate and multivariate predictor of in-hospital and 30-day mortality, and the odds ratios for mortality are nearly identical for TIMI grade 3 flow at 60 and 90 minutes. Thus, the 60-minute angiographic end point appears to be a valid alternative to that at 90 minutes and may permit earlier decisions regarding post-thrombolytic intervention.

Global impairment of coronary blood flow in the setting of acute coronary syndromes (a RESTORE substudy). Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis.

Acute coronary syndromes result in a global impairment of coronary blood flow with nonculprit artery blood flow being associated with culprit artery flow and vice versa. Improvements in nonculprit artery flow are related to improvements in culprit artery flow after percutaneous intervention; nonculprit arteries with abnormal flow sustain greater improvements in their flow after culprit artery intervention.

Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs.

BACKGROUND: Although improved epicardial blood flow (as assessed with either TIMI flow grades or TIMI frame count) has been related to reduced mortality after administration of thrombolytic drugs, the relationship of myocardial perfusion (as assessed on the coronary arteriogram) to mortality has not been examined. METHODS AND RESULTS: A new, simple angiographic method, the TIMI myocardial perfusion (TMP) grade, was used to assess the filling and clearance of contrast in the myocardium in 762 patients in the TIMI (Thrombolysis In Myocardial Infarction) 10B trial, and its relationship to mortality was examined. TMP grade 0 was defined as no apparent tissue-level perfusion (no ground-glass appearance of blush or opacification of the myocardium) in the distribution of the culprit artery; TMP grade 1 indicates presence of myocardial blush but no clearance from the microvasculature (blush or a stain was present on the next injection); TMP grade 2 blush clears slowly (blush is strongly persistent and diminishes minimally or not at all during 3 cardiac cycles of the washout phase); and TMP grade 3 indicates that blush begins to clear during washout (blush is minimally persistent after 3 cardiac cycles of washout). There was a mortality gradient across the TMP grades, with mortality lowest in those patients with TMP grade 3 (2.0%), intermediate in TMP grade 2 (4.4%), and highest in TMP grades 0 and 1 (6.0%; 3-way P=0.05). Even among patients with TIMI grade 3 flow in the epicardial artery, the TMP grades allowed further risk stratification of 30-day mortality: 0.73% for TMP grade 3; 2.9% for TMP grade 2; 5.0% for TMP grade 0 or 1 (P=0.03 for TMP grade 3 versus grades 0, 1, and 2; 3-way P=0.066). TMP grade 3 flow was a multivariate correlate of 30-day mortality (OR 0.35, 95% CI 0.12 to 1.02, P=0.054) in a multivariate model that adjusted for the presence of TIMI 3 flow (P=NS), the corrected TIMI frame count (OR 1.02, P=0.06), the presence of an anterior myocardial infarction (OR 2.3, P=0.03), pulse rate on admission (P=NS), female sex (P=NS), and age (OR 1.1, P<0.001). CONCLUSIONS: Impaired perfusion of the myocardium on coronary arteriography by use of the TMP grade is related to a higher risk of mortality after administration of thrombolytic drugs that is independent of flow in the epicardial artery. Patients with both normal epicardial flow (TIMI grade 3 flow) and normal tissue level perfusion (TMP grade 3) have an extremely low risk of mortality.

Determinants of coronary blood flow after thrombolytic administration. TIMI Study Group. Thrombolysis in Myocardial Infarction.

OBJECTIVES: This study evaluated the determinants of coronary blood flow following thrombolytic administration in a large cohort of patients. BACKGROUND: Tighter residual stenoses following thrombolysis have been associated with slower coronary blood flow, but the independent contribution of other variables to delayed flow has not been fully explored. METHODS: The univariate and multivariate correlates of coronary blood flow at 90 min after thrombolytic administration were examined in a total of 2,195 patients from the Thrombolysis in Myocardial Infarction (TIMI) 4, 10A, 10B and 14 trials. The cineframes needed for dye to first reach distal landmarks (corrected TIMI frame count, CTFC) were counted as an index of coronary blood flow. RESULTS: The following were validated as univariate predictors of delayed 90-min flow in two cohorts of patients: a greater percent diameter stenosis (p < 0.0001 for both cohorts), a decreased minimum lumen diameter (p = 0.0003, p = 0.0008), a greater percent of the culprit artery distal to the stenosis (p = 0.03, p = 0.02) and the presence of any of the following: delayed achievement of patency (i.e., between 60 and 90 min) (p < 0.0001 for both cohorts), a culprit location in the left coronary circulation (left anterior descending or circumflex) (p = 0.02, p < 0.0001), pulsatile flow (i.e., reversal of flow in systole, a marker of heightened microvascular resistance, p = 0.0003, p < 0.0001) and thrombus (p = 0.002, p = 0.03). Despite a minimal 16.4% residual stenosis following stent placement, the mean post-stent CTFC (25.8 +/- 17.2, n = 181) remained significantly slower than normal (21.0 +/- 3.1, n = 78, p = 0.02), and likewise 34% of patients did not achieve a CTFC within normal limits (i.e., <28 frames, the upper limit of the 95th percent confidence interval previously reported for normal flow). Those patients who failed to achieve normal CTFCs following stent placement had a higher mortality than did those patients who achieved normal flow (6/62 or 9.7% vs. 1/118 or 0.8%, p = 0.003). CONCLUSIONS: Lumen geometry is not the sole determinant of coronary blood flow at 90 min following thrombolytic administration. Other variables such as the location of the culprit artery, the duration of patency, a pulsatile flow pattern and thrombus are also related to slower flow. Despite a minimal 16% residual stenosis, one-third of the patients treated with adjunctive stenting still have a persistent flow delay following thrombolysis, which carries a poor prognosis.

Impaired coronary blood flow in nonculprit arteries in the setting of acute myocardial infarction. The TIMI Study Group. Thrombolysis in myocardial infarction.

OBJECTIVES AND BACKGROUND: While attention has focused on coronary blood flow in the culprit artery in acute myocardia infarction (MI), flow in the nonculprit artery has not been studied widely, in part because it has been assumed to be normal. We hypothesized that slower flow in culprit arteries, larger territories infarcted and hemodynamic perturbations may be associated with slow flow in nonculprit arteries. METHODS: The number of frames for dye to first reach distal landmarks (corrected TIMI [Thrombolysis in Acute Myocardial Infarction] frame count [CTFC]) were counted in 1,817 nonculprit arteries from the TIMI 4, 10A, 10B and 14 thrombolytic trials. RESULTS: Nonculprit artery flow was slowed to 30.9 +/- 15.0 frames at 90 min after thrombolytic administration, which is 45% slower than normal flow in the absence of acute MI (21 +/- 3.1, p < 0.0001). Patients with TIMI grade 3 flow in the culprit artery had faster nonculprit artery CTFCs than those patients with TIMI grades 0, 1 or 2 flow (29.1 +/- 13.7, n = 1,050 vs. 33.3 +/- 16.1, n = 752, p < 0.0001). The nonculprit artery CTFC improved between 60 and 90 min (3.3 +/- 17.9 frames, n = 432, p = 0.0001), and improvements were related to improved culprit artery flow (p = 0.0005). Correlates of slower nonculprit artery flow included a pulsatile flow pattern (i.e., systolic flow reversal) in the nonculprit artery (p < 0.0001) and in the culprit artery (p = 0.01), a left anterior descending artery culprit artery location (p < 0.0001), a decreased systolic blood pressure (p = 0.01), a decreased ventriculographic cardiac output (p = 0.02), a decreased double product (p = 0.0002), a greater percent diameter stenosis of the nonculprit artery (p = 0.01) and a greater percent of the culprit artery bed lying distal to the stenosis (p = 0.04). Adjunctive percutaneous transluminal coronary angioplasty (PTCA) of the culprit artery restored a culprit artery CTFC (30.4 +/- 22.2) that was similar to that in the nonculprit artery at 90 min (30.2 +/- 13.5), but both were slower than normal CTFCs (21 +/- 3.1, p < 0.0005 for both). If flow in the nonculprit artery was abnormal (CTFC > or = 28 frames) then the CTFC after PTCA in the culprit artery was 17% slower (p = 0.01). Patients who died had slower global CTFCs (mean CTFC for the three arteries) than patients who survived (46.8 +/- 21.3, n = 47 vs. 39.4 +/- 16.7, n = 1,055, p = 0.02). CONCLUSIONS: Acute MI slows flow globally, and slower global flow is associated with adverse outcomes. Relief of the culprit artery stenosis by PTCA restored culprit artery flow to that in the nonculprit artery, but both were 45% slower than normal flow.

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

Angiographic methods to assess human coronary angiogenesis.

It is unclear how agents designed to promote angiogenesis in the human heart affect the arteriographic appearance of the collateral circulation. Possible changes in collateral vessels include new collateral vessels arising from epicardial arteries, new branches emanating from existing collateral vessels, wider or longer collateral vessels, and higher dye transit rates that result in improved recipient vessel filling. Given the multiple mechanisms by which these new agents may improve myocardial perfusion, a rigorous, systematic, and comprehensive analysis of coronary arteriograms is required to discern the true mechanism of benefit. The method of analysis must account for potential changes in collateral blood flow, number, branching pattern, and length as well as changes in recipient vessel filling. The ability to detect differences between intricate networks of vessels in an angiographic study is dependent on maintaining consistency in cinefilming as well as the core laboratory methods between time points. In this report, we describe the methodology our angiographic core laboratory has found to be most effective to evaluate these very complex angiograms and attempt to capture all the possible modalities of angiogenesis.

Thrombolysis in Myocardial Infarction frame count in saphenous vein grafts.

BACKGROUND: Although the Thrombolysis in Myocardial Infarction flow grade system is a widely used index of coronary blood flow, it has important limitations. We recently described a new continuous measure of blood flow in native coronary arteries, the Thrombolysis in Myocardial Infarction frame count (TFC), and sought to extend this method to coronary artery bypass grafts. METHODS: We retrospectively analyzed cinefilms of patients' status after coronary artery bypass grafting, excluding patients with recent myocardial infarction and grafts with stenoses in the graft or native vessel. We counted the cineframes required for dye to travel from the ostium of the graft to the graft anastomotic site (TFCg) and to a standardized distal coronary landmark (TFC). RESULTS: For all vein grafts combined, TFCg was 19.2+/-5.7 frames (mean+/-SD, n = 93) and the TFC was 33.9+/-8.0 frames (n = 67). The upper limits for "normal" flow, calculated from the 95% confidence intervals, were 31 frames for TFCg and 50 frames for TFC. CONCLUSIONS: The Thrombolysis in Myocardial Infarction frame counting method has now been extended to normal saphenous vein grafts, and normal reference values are provided.

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.

Angioplasty guidewire velocity: a new simple method to calculate absolute coronary blood velocity and flow.

The Thrombolysis In Myocardial Infarction (TIMI) frame count is a relative index of coronary flow that measures time by counting the number of frames required for dye to travel from the ostium to a standardized coronary landmark in a cineangiogram filmed at a known speed (frames/s). We describe a new method to measure distance along arteries so that absolute velocity (length divided by time) and absolute flow (area x velocity) may be calculated in patients undergoing percutaneous transluminal coronary angiography (PTCA). After PTCA, the guidewire tip is placed at the coronary landmark and a Kelly clamp is placed on the guidewire where it exits the Y-adapter. The guidewire tip is then withdrawn to the catheter tip and a second Kelly clamp is placed on the wire where it exits the Y-adapter. The distance between the 2 Kelly clamps outside the body is the distance between the catheter tip and the anatomic landmark inside the body. Velocity (cm/s) may be calculated as this distance (cm) divided by TIMI frame count (frames) x film frame speed (frames/s). Flow (ml/s) may be calculated by multiplying this velocity (cm/s) and the mean cross-sectional lumen area (cm2) along the length of the artery to the TIMI landmark. In 30 patients, velocity increased from 13.9 +/- 8.5 cm/s before to 22.8 +/- 9.3 cm/s after PTCA (p <0.001). Despite TIMI grade 3 flow both before and after PTCA in 18 patients, velocity actually increased 38%, from 17.0 +/- 5.4 to 23.5 +/- 9.0 cm/s (p = 0.01). For all 30 patients, flow doubled from 0.6 +/- 0.4 ml/s before to 1.2 +/- 0.6 ml/s after PTCA (p <0.001). In the 18 patients with TIMI grade 3 flow both before and after PTCA, flow increased 86%, from 0.7 +/- 0.3 to 1.3 +/- 0.6 ml/s (p = 0.001). Distance along coronary arteries (length) can be simply measured using a PTCA guidewire. This length may be combined with the TIMI frame count to calculate measures of absolute velocity and flow that are sensitive to changes in perfusion. TIMI grade 3 flow is composed of a range of velocities and flows.

TIMI frame count: a quantitative method of assessing coronary artery flow.

BACKGROUND: Although the Thrombolysis in Myocardial Infarction (TIMI) flow grade is valuable and widely used qualitative measure in angiographic trials, it is limited by its subjective and categorical nature. METHODS AND RESULTS: In normal patients and patients with acute myocardial infarction (MI) (TIMI 4), the number of cineframes needed for dye to reach standardized distal landmarks was counted to objectively assess an index of coronary blood flow as a continuous variable. The TIMI frame-counting method was reproducible (mean absolute difference between two injections, 4.7 +/- 3.9 frames, n=85). In 78 consecutive normal arteries, the left anterior descending coronary artery (LAD) TIMI frame count (36.2 +/- 2.6 frames) was 1.7 times longer than the mean of the right coronary artery (20.4 +/- 3.0) and circumflex counts (22.2 +/- 4.1, P < .001 for either versus LAD). Therefore, the longer LAD frame counts were corrected by dividing by 1.7 to derive the corrected TIMI frame count (CTFC). The mean CTFC in culprit arteries 90 minutes after thrombolytic administration followed a continuous unimodal distribution (there were not subpopulations of slow and fast flow) with a mean value of 39.2 +/- 20.0 frames, which improved to 31.7 +/- 12.9 frames by 18 to 36 hours (P < .001). No correlation existed between improvements in CTFCs and changes in minimum lumen diameter (r=-.05, P=.59). The mean 90-minute CTFC among nonculprit arteries (25.5 +/- 9.8) was significantly higher (flow was slower) compared with arteries with normal flow in the absence of acute MI (21.0 +/- 3.1, P < .001) but improved to that of normal arteries by 1 day after thrombolysis (21.7 +/- 7.1, P=NS). CONCLUSIONS: The CTFC is a simple, reproducible, objective and quantitative index of coronary flow that allows standardization of TIMI flow grades and facilitates comparisons of angiographic end points between trials. Disordered resistance vessel function may account in part for reductions in flow in the early hours after thrombolysis.