(Circulation. 1999;99:1945-1950.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Relationship Between TIMI Frame Count and Clinical Outcomes After Thrombolytic Administration
From the Cardiovascular Division of the Department of Medicine, the Allegheny General Hospital, Pittsburgh, Pa (C.M.G., S.A.M., M.J.R., K.A.R., S.J.M.); Leuven University, Leuven, Belgium (F.V.d.W.); and Brigham & Women's Hospital, Boston, Mass (C.H.M., C.P.C., E.B.).
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
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 
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 
40% was 13.0% among patients with TIMI grade 3
flow (CTFC 40), the CTFC tended to segregate patients into lower-risk
(CTFC 20, risk of adverse outcome of 7.9%) and higher-risk
subgroups (CTFC >20 to 40, risk of adverse outcome of 15.5%;
P=0.17).
Conclusions—Faster (lower) 90-minute CTFCs are related to
improved in-hospital and 1-month clinical outcomes after
thrombolytic administration in both
univariate and multivariate models. Even
among those patients classified as having normal flow (TIMI grade 3
flow, CTFC 40), there may be lower- and higher-risk subgroups.
Key Words: thrombolysis • myocardial infarction • blood flow • TIMI frame count
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The conventional Thrombolysis In Myocardial Infarction (TIMI) flow grade classification scheme1 has been a valuable tool to compare angiographic and clinical outcomes after thrombolysis.2 3 4 5 6 7 However, this classification scheme is limited by interobserver variability, its categorical nature, its limited statistical power, and the fact that nonculprit flow (used to gauge TIMI grade 3 flow) is abnormal.8 Recently, we described a new index of coronary blood flow called the corrected TIMI frame count (CTFC), in which the number of frames required for dye to reach standardized distal landmarks is counted.8 We hypothesized that faster flow (lower CTFCs) would be related to improved clinical outcomes.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
A total of 1248 patients from the TIMI 4, 10A, and 10B trials had CTFC and outcomes data available for analysis. The TIMI 4 trial was a randomized, double-blind comparison of 3 thrombolytic regimens in 416 patients9 : anistreplase (Eminase or APSAC, 30 U IV), front-loaded recombinant tissue plasminogen activator (rtPA) (Activase or alteplase), or combination therapy. The TIMI 10A trial was a nonrandomized, open-label study of 8 ascending doses of TNK (5, 7.5, 10, 15, 20, 30, 40, and 50 mg IV over 5 seconds) in 113 patients.10 TIMI 10B was a randomized comparison of TNK (30, 40, and 50 mg) and 90-minute infusion of rtPA (Activase or alteplase) in 854 patients.11 Angiography was performed at 60, 75, and 90 minutes after thrombolysis.8 9 10 11 Nitroglycerin was administered every 15 minutes if the systolic blood pressure exceeded 110 mm Hg.8 9 10 11
Assessment of Flow
TIMI flow grade was assessed at an angiographic core laboratory
as previously defined.1 The CTFC is the number of cine
frames required for contrast to first reach standardized distal
coronary landmarks in the culprit artery and is measured with a
frame counter on a cine viewer.8 A frame count of 100, a
value that is the 99th percentile of patent vessels, was imputed to an
occluded vessel.8 CTFC is a measure of time, and data were
converted when necessary to be based on the most common filming speed
used in the United States (30 frames/s). The CTFC was divided by 30 to
calculate the transit time for dye to traverse the length of the artery
to the landmark in seconds and multiplied by 1000 to calculate the time
in milliseconds. This was used along with the heart rate to calculate
the fraction of a cardiac cycle required for dye to traverse the
artery: fraction of cardiac cycle=(CTFC/30 seconds)/(60 seconds/heart
rate). Calculation of the fraction of a cardiac cycle required for dye
to traverse the culprit artery normalizes the CTFC for heart rate.
Statistical Analysis
In-hospital mortality and recurrent myocardial infarction (MI)
were ascertained in all 3 trials (TIMI 4, 10A, and 10B). A composite
end point was ascertained in TIMI 4 and TIMI 10A and consisted of any
of the following in-hospital adverse events: death; recurrent MI;
development of new severe congestive heart failure (CHF) or
shock; or ejection fraction <40%. In TIMI 4, a predischarge ejection
fraction was obtained, and in TIMI 10A, a 90-minute ejection fraction
was obtained. Mortality and morbidity committees confirmed all adverse
events. Analyses were performed with STATA statistical
software.12 Variables were compared by Fisher's exact
test for categorical data and ANOVA for continuous variables. The
nonparametric Wilcoxon rank sum test was used to
compare continuous variables that were not normally distributed.
Data are summarized as mean±SD. Due to the relatively small number of
deaths (n=53) in the sample of 1248 patients, the 5 most significant
clinical and angiographic univariate predictors of
in-hospital mortality (one for each 10 events) with a value of
P<0.01 were entered into multivariate
models. A linear spline analysis was performed to reject the
null hypothesis that the slope of the relationship between the CTFC and
outcomes remained constant across intervals of the CTFC: 0 to 20, 21 to
40, 41 to 60, 61 to 80, and 
81. Fractional polynomial regression was
also used to determine if the use of a higher-order polynomial
(quadratic, cubic, or greater) was superior to linear regression in
fitting the relationship between outcomes and the CTFC as a continuous
variable.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Univariate Predictors of In-Hospital Mortality
The 5 univariate correlates (Table 1
) that successfully competed for
entry into the multivariate model of in-hospital
mortality (Tables 2 and 3) included age
(
2=63.9, P<0.001), CTFC
(2=17.3, P<0.001), anterior MI
location (2=12.5, P<0.001), heart
rate (2=9.3, P<0.001), and female
sex (2=8.3, P=0.003). TIMI flow
grades and CTFC were colinear, and TIMI flow grades were dropped from
the model.
|
|
|
Relationship of TIMI Frame Count to Mortality
The CTFC method was introduced during the TIMI 4 trial, and in
this exploratory data set, the 90-minute CTFC was a
univariate predictor of in-hospital mortality (OR=1.24
expressed per 10-frame rise throughout; 95% CI, 1.1 to 1.4;
P=0.007; n=318). This observation was then prospectively
validated in the TIMI 10 trials (OR=1.16; 95% CI, 1.1 to 1.3;
P=0.002; n=930). In all 3 trials combined, the CTFC was a
univariate predictor of in-hospital mortality (OR=1.18;
95% CI, 1.1 to 1.3; P<0.001). When the percent change in
the CTFC was used instead, the OR was 1.07 for every 20% increase in
the CTFC (P<0.001).
Patients who died in the hospital had higher CTFCs (69.6±35.4 [n=53]
versus 49.5±32.3 [n=1195]; P=0.0003) (Figure 1). When the analysis was
performed with either the CTFC at 90 minutes after
thrombolytic administration or, if the patient went on
to have an intervention, immediately after 90-minute angiography
(rescue or adjunctive percutaneous intervention
[PCI]), the CTFC at the completion of any and all therapy (the final
CTFC) was also significantly higher in patients who died in the
hospital (53.0±36.7 [n=45] versus 38.4±25.9 [n=1110];
P=0.03).
|
The CTFC identified a subgroup of patients at particularly low
mortality risk among those classified as having normal flow. 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% (18/658) 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 versus 2 flow),8 to 6.4% (35/549) in
patients with a CTFC >40 (3-way P=0.003) (Figure 2).
|
The 90-minute CTFC (OR=1.21; z=4.29; P<0.001), the final CTFC (OR=1.15; z=2.81; P=0.005), the fraction of the cardiac cycle (OR=1.46; P<0.001), and the dye transit time in seconds (OR=1.64; P<0.001) were each independent predictors of in-hospital mortality even when the 4 other most significant variables (age, heart rate, anterior MI, and female sex) were adjusted for in multivariate models. When the analysis was confined to the 881 patients who did not undergo PCI, the 90-minute CTFC (OR=1.15; z=2.43; P=0.02) was a multivariate predictor of in-hospital mortality. The 90-minute CTFC was also related to mortality later, at 30 to 42 days (OR=1.15; P<0.001), and likewise, the 90-minute CTFC was higher for patients who died at 30 to 42 days than for those who lived (66.2±36.4 [n=57] versus 49.9±32.1 [n=1059]; P=0.006).
When the conventional TIMI flow grades were used instead of CTFC data, TIMI grade 0/1 flow differed significantly from TIMI grade 3 flow (OR=4.4; P<0.001), but TIMI grade 2 flow did not differ from TIMI grade 3 flow (OR=0.6; P=NS) in the multiple logistic regression model.
Comparison of 60-, 75-, and 90-Minute TIMI Frame Count Data in
Predicting Mortality
To ensure a consistent sample size and statistical power,
clinical outcomes were compared in the 563 patients in whom the CTFC
was assessed at all 3 time points. Although the 90-minute CTFC was
associated with mortality (OR=1.12; P=0.049) neither the
75-minute CTFC (OR=1.07; P=0.24) nor the 60-minute CTFC
(OR=1.08; P=0.21) achieved significance. The mortality rate
for patients with an occluded artery at 60 minutes (6.1%, 12/197)
tended to be lower than that for patients with an occluded artery at 90
minutes (10.2%, 29/284; P=0.14). Patients with an occluded
artery at 60 minutes that opened by 90 minutes had a mortality rate of
0.0% (0/49), which was lower than the 8.2% (12/146) mortality rate
for those whose arteries remained occluded at both 60 and 90 minutes
(P=0.05).
Relationship Between CTFC and Death or Recurrent MI
The CTFC for patients who died or sustained a recurrent MI was
significantly higher (60.0±34.7 [n=100] versus 49.5±32.4
[n=1144]; P=0.01) (Figure 3), as was the final CTFC (47.5±33.3
[n=89] versus 38.2±25.8 [n=1066]; P=0.05). The
90-minute CTFC (OR=1.10; z=3.17; P=0.002), the
final CTFC (OR=1.11; z=2.78; P=0.005), the
fraction of the cardiac cycle (OR=1.18; P=0.01), and the dye
transit time (OR=1.35; P=0.002) were all
multivariate predictors of death/recurrent MI. When the
analysis was confined to the 881 patients who did not undergo
PCI, the 90-minute CTFC (OR=1.10; P=0.04) was a
multivariate predictor of death/recurrent MI.
|
When the conventional TIMI flow grades were used instead of the CTFC, TIMI grade 0/1 differed from TIMI grade 3 flow (OR=4.4; P<0.001), but TIMI grade 2 flow did not differ from TIMI grade 3 flow (OR=0.6; P=NS) in the multiple logistic regression model.
Relationship Between CTFC and Composite Adverse Events
The 90-minute CTFC for patients with any adverse outcome (death,
recurrent MI, shock/severe CHF, or left ventricular
ejection fraction <40%) was significantly higher than that for
patients without an event (66.3±36.9 [n=83] versus 52.4±31.9
[n=341]; P=0.002) (Figure 4), as was the final CTFC (55.8±33.7
[n=74] versus 41.4±26.1 [n=316]; P=0.0006). The
90-minute CTFC (OR=1.13; z=3.13; P=0.003), the
final CTFC (OR=1.13; z=2.56; P=0.01), the
fraction of the cardiac cycle (OR=1.30; P=0.002), and the
dye transit time (OR=1.45; P=0.003) were
multivariate predictors of adverse outcomes. When the
analysis was confined to those patients who did not undergo
PCI, the 90-minute CTFC (OR=1.13; P=0.02) was a
multivariate predictor of adverse outcomes.
|
When the conventional TIMI flow grades were used instead of frame count
data, TIMI grade 0/1 differed from TIMI grade 3 flow (OR=2.3;
P=0.006), and TIMI grade 2 flow differed from TIMI grade 3
flow (OR=1.9; P=0.02) in the multiple logistic regression
model. Within the categories of TIMI grade 2 and 3 flows, the CTFC was
a multivariate predictor of adverse outcomes (OR=1.17;
P=0.015). Figure 5 shows the
risk of adverse outcomes within the categories of TIMI 2 and 3 flow.
Although the overall rate of adverse outcomes for TIMI grade 3 flow was
13.0% (33 of 253 patients), those patients with a CTFC 20 had
an incidence of 7.9% (3 of 38), and those with a CTFC >20 and 40
(the previously defined upper bound of TIMI grade 3 flow) tended to
have a higher incidence at 15.5% (26 of 168 patients;
P=0.17).
|
Linearity of Relationship Between CTFC and Clinical
Outcomes
A linear spline analysis failed to reject the null
hypothesis that there was a linear relationship between the CTFC and
outcomes (ie, the null hypothesis that the ORs were the same across
intervals of the CTFC was not rejected). A logarithmic transformation
of the CTFC data provided no better explanatory power in any of the
outcome variables. Fractional polynomial regression demonstrated
that the use of a higher-order polynomial (quadratic, cubic, or
greater) was not superior to linear regression in fitting the
relationship between outcomes and the CTFC as a continuous
variable.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Higher CTFCs 90 minutes after thrombolytic administration are associated with an increased risk of mortality and composite end points in both univariate and multivariate models. This was true of events in the hospital and by 30 to 42 days after treatment. These findings extend those of the Global Utilization of Streptokinase and TPA for Occluded Arteries (GUSTO) angiographic investigators, who have reported that patients with TIMI grade 3 flow have improved outcomes compared with patients with TIMI grade 2 flow at 90 minutes.3 The use of the CTFC identifies a subgroup of patients with TIMI grade 3 flow who are at extremely low risk of mortality: none of those patients who achieved a CTFC <14 after thrombolysis died (TIMI grade 4 flow, or flow that is faster than the 95th percentile for normal flow). Likewise, in the setting of PTCA for acute coronary syndromes (1057 trial patients in the Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis [RESTORE] trial), we have recently demonstrated that survivors had a lower CTFC (faster flow) than patients who died after PTCA, and none of the 376 patients with a CTFC <14 after PTCA (hyperemic flow or TIMI grade 4 flow) died.13 14 With respect to the composite end point of death, recurrent MI, shock, or left ventricular ejection fraction <40%, the CTFC was a multivariate predictor of adverse outcomes (P=0.015) among patients with TIMI grade 2 and 3 flows in a model that controlled for age, anterior MI, heart rate, and sex. Even within TIMI grade 3, there tended to be lower- and higher-risk subgroups: a CTFC
20 was associated with a risk of adverse outcome of
7.9%, whereas a CTFC >20 to 40 was associated with a risk of
adverse outcome of 15.5% (Figure 4
). Thus, although the TIMI
flow grades and the TIMI frame count are colinear and therefore do not
appear to provide independent predictive power when combined in the
same multivariate model, this analysis suggests
that the CTFC may add additional prognostic information within TIMI
grade 3 flow. The observation that the CTFC is an independent
multivariate correlate of outcomes also extends
observations from GUSTO I by Lee et al15 in which
nonangiographic clinical variables such as age, heart rate, and
anterior location of the MI were demonstrated to be
multivariate determinants of mortality. When we
normalized the CTFC for heart rate by estimating the fraction of a
cardiac cycle required for the dye to reach the landmark, this index of
flow was also related to clinical outcomes in
multivariate models.
In GUSTO I, a 20 percentage point or a 64% relative improvement in the
rate of TIMI grade 3 flow of rtPA over streptokinase (54% versus 33%)
was associated with a 1% improvement in mortality.3 The
corresponding analysis using the CTFC in these 3 TIMI trials
indicates that a 20% relative improvement in the CTFC would alter
mortality by a factor of 1.07 or by 0.3% (overall mortality was
4.25% in these trials), and a 64% improvement would therefore reduce
mortality by another 1%. Thus, the mortality benefits estimated by the
relative improvements in the TIMI flow grades and the TIMI frame count
closely parallel each other.
This analysis assumes that there is a linear relationship between 90-minute coronary blood flow and mortality, and likewise, the results in this study are presented as the OR for every 10-frame rise in the CTFC. A linear spline analysis failed to reject the null hypothesis that there was a linear relationship between the CTFC and outcomes (ie, the null hypothesis that the ORs were the same across intervals of the CTFC was not rejected). Furthermore, neither a logarithmic transformation of the CTFC data nor the use of higher-order polynomials to fit the relationship to complex curves provided any better explanatory power in any of the outcome variables. The number of events in these trials, however, was rather small, and it is possible that a larger number of events might demonstrate that the relationship between flow and mortality improvements is instead nonlinear.
Many patients in thrombolytic trials now undergo angiography by 60 minutes, and the relative merits of waiting to obtain 90-minute angiographic data over 60-minute data are unclear. This study demonstrates that in a data set with both 60- and 90-minute data available, the conventional 90-minute end point was related to mortality, whereas the 60-minute data were not. Although this could be interpreted as demonstrating the superiority of 90-minute angiography as a surrogate end point, this interpretation must be weighed carefully in light of the observation that patients whose closed arteries failed to open spontaneously between 60 and 90 minutes had a significantly higher mortality than those patients whose arteries did open spontaneously (without intervention) between 60 and 90 minutes (0% versus 8.2%; P=0.05). Although these observations suggest that reperfusion between 60 and 90 minutes is related to improved outcomes, randomized trial data are lacking regarding the clinical benefit of percutaneous intervention for an occluded artery at 60 rather than 90 minutes after administration of a thrombolytic. If newer pharmacological reperfusion strategies can demonstrate superiority at 60 minutes rather than waiting until 90 minutes, this may obviate the need for 90-minute angiography. Indeed, data from the TIMI 14 trial suggest that there is a greater advantage in CTFCs at 60 minutes for the combination of abciximab plus reduced-dose tPA versus front-loaded tPA (14 frames, P=0.001) compared with 90 minutes (7 frames, P=0.005).16
Another issue that has arisen is whether use of the CTFC at 90 minutes is superior to use of the final posttreatment CTFC (ie, either the CTFC at 90 minutes after thrombolytic administration or, if the patient went on to have an intervention [rescue or adjunctive PTCA or stent], the CTFC at the completion of the intervention). For all outcomes, the 90-minute CTFC had higher z values and more significant probability values in relationship to clinical outcomes than the final posttreatment CTFC.
Limitations
When prospectively applied in the TIMI 10 trials, the CTFC
was evaluable in 97.1% of open arteries (741 of 763). The mortality
rate in patients with CTFC data available (4.3%, 53 of 1248) was no
different from that in the study group overall (4.3%, 60 of 1383).
These mortality rates may be lower than those observed outside of
randomized trials because of the selective nature of the
inclusion/exclusion criteria. Rescue and adjunctive angioplasty may
have obscured differences in outcomes that would have been attributable
to 90-minute flow, but the same relationships were observed when the
analysis was confined to those patients who did not undergo
interventions. Although 90-minute coronary blood flow is
related to mortality, other causes of death such as intracranial
hemorrhage, reinfarction, ventricular
arrhythmias, and mechanical complications may be unrelated to
90-minute blood flow.
Conclusions
Higher CTFCs at 90 minutes after thrombolytic
administration are related to an increased risk of early and late
adverse outcomes in both univariate and
multivariate models. The CTFC may add additional
prognostic information by segregating patients with TIMI grade 3 flow
into lower- and higher-risk subgroups.
|
Acknowledgments |
|---|
This study was supported in part by grants from Smith Kline Beecham, Philadelphia, Pa, Genentech, Inc, South San Francisco, Calif, and Boehringer Ingelheim, Rhein, Germany.
|
Footnotes |
|---|
Reprint requests to C. Michael Gibson, MS, MD, Director of Invasive Cardiology, Allegheny General Hospital, 320 E North Ave, Pittsburgh, PA 15212.
Received August 12, 1998; revision received November 6, 1998; accepted January 11, 1999.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. The TIMI Study Group. The Thrombolysis In Myocardial Infarction (TIMI) trial. N Engl J Med. 1985;31:932–936.
2.
The GUSTO Investigators. An international randomized
trial comparing four thrombolytic strategies for acute
myocardial infarction. N Engl J Med. 1993;329:673–682.
3.
The GUSTO Angiographic Investigators. The effects of
tissue plasminogen activator, streptokinase, or
both on coronary artery patency, ventricular
function, and survival after acute myocardial infarction. N
Engl J Med. 1993;329:1615–1622.
4. Van de Werf F. Discrepancies between the effects of coronary reperfusion on survival and left ventricular function. Lancet. 1989;1:1367–1369.[Medline] [Order article via Infotrieve]
5. Vogt A, Von Essen R, Tebbe U, Feuerer W, Appel KF, Neuhaus KL. Impact of early perfusion status of the infarct-related artery on short-term mortality after thrombolysis for acute myocardial infarction: retrospective analysis of four German multicenter studies. J Am Coll Cardiol. 1993;21:1391–1395.[Abstract]
6. Karagounis L, Sorensen SG, Menlove RI, Moreno F, Anderson JL. Does thrombolysis in myocardial infarction TIMI perfusion grade 2 represent a mostly patent artery or a mostly occluded artery? Enzymatic and electrocardiographic evidence from the TEAM-2 study. J Am Coll Cardiol. 1992;17:1–10.
7.
Anderson JL, Karagounis LA, Becker LC, Sorensen SG,
Menlove RL, for the TEAM-3 Investigators. TIMI perfusion grade 3 but
not grade 2 results in improved outcome after
thrombolysis for myocardial infarction:
ventriculographic, enzymatic, and electrocardiographic evidence from
the TEAM-3 study. Circulation. 1993;87:1829–1839.
8.
Gibson CM, Cannon CP, Daley WL, Dodge JT, Alexander B,
Marble SJ, McCabe CH, Raymond L, Fortin T, Poole WK, Braunwald E. The
TIMI frame count: a quantitative method of assessing coronary
artery flow. Circulation. 1996;93:879–888.
9. Cannon CP, McCabe CH, Diver DJ, Herson S, Greene RM, Shah PK, Sequeira RF, Leya F, Kirshenbaum JM, Magorien RD, Palmeri S, Davis V, Gibson CM, Poole WK, Braunwald E, for the TIMI 4 Investigators. Comparison of front-loaded recombinant tissue-type plasminogen activator, anistreplase and combination thrombolytic therapy for acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) 4 trial. J Am Coll Cardiol. 1994;24:1602–1610.[Abstract]
10.
Cannon CP, McCabe CH, Gibson CM, Ghali M,
Sequeira RF, McKendall GR, Breed J, Modi NB, Fox NL, Tracy RP, Love TW,
Braunwald E, and the TIMI 10A Investigators. TNK-tissue
plasminogen activator in acute myocardial
infarction: results of the Thrombolysis In Myocardial
Infarction (TIMI) 10A dose-ranging trial. Circulation. 1997;95:351–356.
11.
Cannon CP, Gibson CM, McCabe CH, Adgey AAJ, Schweiger
MJ, Sequeira RF, Grollier G, Giugliano RP, Frey M, Mueller HS,
Steingart RM, Fox NL, Weaver WD, Van de Werf F, Braunwald E, for the
TIMI 10B Investigators. TNK-tissue plasminogen
activator compared with front-loaded alteplase in acute
myocardial infarction: results of the TIMI 10B Trial.
Circulation.. 1998;98:2805–2814.
12. Stata Corp. Stata Statistical Software: Release 5.0. College Station, Tex: Stata Corp; 1997.
13.
Gibson CM, Goel M, Cohen DE, Piana RN, Deckelbaum LI,
Harris KE, King SB, for the RESTORE Investigators. Six month
angiographic and clinical outcomes following IIb/IIIa blockade with
tirofiban. J Am Coll Cardiol. 1998;32:28–34.
14. Gibson CM, Goel M, Dotani I, Rizzo MJ, McLean C, Martin NE, Al-Mousa EN, Marble SJ, Daley WL, Dodge T. The post-PTCA TIMI frame count and mortality in RESTORE. Circulation. 1996;94(suppl I):I-85. Abstract.
15.
Lee KL, Woodlief LH, Topol EJ, Weaver DW, Betriu A, Col
J, Simoons M, Aylward P, Van de Werf F, Maliff RM. Predictors of 30-day
mortality in the era of reperfusion for acute myocardial infarction:
results from an international trial of 41 021 patients.
Circulation. 1995;91:1659–1668.
16. Gibson M, Giugliano RP, Anderson K, Scherer JC, McCabe CH, Antman EM. Abciximab enhances thrombolysis. a comparison of abciximab alone versus abciximab plus low dose thrombolytics using the corrected TIMI frame count. Circulation. 1998;98(suppl):I-559. Abstract.
This article has been cited by other articles:
 |
|
 |
|
  R. Y. Kwong and M. A. Pfeffer Infarct haemorrhage detected by cardiac magnetic resonance imaging: are we seeing the latest culprit in adverse left ventricular remodelling? Eur. Heart J., June 2, 2009; 30(12): 1431 - 1433. [Full Text] [PDF]
|
|
|
|
 |
|
 C.-H. Lee, S.-M. Khoo, B.-C. Tai, E. Y. Chong, C. Lau, Y. Than, D.-X. Shi, L.-C. Lee, A. Kailasam, A. F. Low, et al. Obstructive Sleep Apnea in Patients Admitted for Acute Myocardial Infarction: Prevalence, Predictors, and Effect on Microvascular Perfusion Chest, June 1, 2009; 135(6): 1488 - 1495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Brener, D. J. Moliterno, P. E. Aylward, A. W.J. van't Hof, W. Ruzyllo, W. W. O'Neill, C. W. Hamm, C. M. Westerhout, C. B. Granger, P. W. Armstrong, et al. Reperfusion after primary angioplasty for ST-elevation myocardial infarction: predictors of success and relationship to clinical outcomes in the APEX-AMI Angiographic Study Eur. Heart J., May 1, 2008; 29(9): 1127 - 1135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Wilson and J. T. Willerson Myocardial Revascularization with Percutaneous Devices Card. Surg. Adult, January 1, 2008; 3(2008): 573 - 598. [Full Text]
|
|
|
|
 |
|
 M. Sezer, H. Oflaz, T. Goren, I. Okcular, B. Umman, Y. Nisanci, A. K. Bilge, Y. Sanli, M. Meric, and S. Umman Intracoronary Streptokinase after Primary Percutaneous Coronary Intervention N. Engl. J. Med., May 3, 2007; 356(18): 1823 - 1834. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Ndrepepa, A. Kastrati, J. Mehilli, F.-J. Neumann, J. ten Berg, O. Bruskina, F. Dotzer, M. Seyfarth, J. Pache, J. Dirschinger, et al. Age-Dependent Effect of Abciximab in Patients With Acute Coronary Syndromes Treated With Percutaneous Coronary Interventions Circulation, November 7, 2006; 114(19): 2040 - 2046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Vijayalakshmi, V J Whittaker, B Kunadian, J Graham, R A Wright, J A Hall, A Sutton, and M A de Belder Prospective, randomised, controlled trial to study the effect of intracoronary injection of verapamil and adenosine on coronary blood flow during percutaneous coronary intervention in patients with acute coronary syndromes Heart, September 1, 2006; 92(9): 1278 - 1284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kaltoft, M. Bottcher, S. S. Nielsen, H.-H. T. Hansen, C. Terkelsen, M. Maeng, J. Kristensen, L. Thuesen, L. R. Krusell, S. D. Kristensen, et al. Routine Thrombectomy in Percutaneous Coronary Intervention for Acute ST-Segment-Elevation Myocardial Infarction: A Randomized, Controlled Trial Circulation, July 4, 2006; 114(1): 40 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. W. Aude and J. L. Mehta Do we need continuous ECG monitoring in patients transferred for primary angioplasty? Eur. Heart J., February 1, 2006; 27(3): 249 - 250. [Full Text] [PDF]
|
|
|
|
|
|
Part 8: Stabilization of the Patient With Acute Coronary Syndromes Circulation, December 13, 2005; 112(24_suppl): IV-89 - IV-110. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ferenc and F.-J. Neumann Efficacy of primary PCI: the microvessel perspective Eur. Heart J. Suppl., October 1, 2005; 7(suppl_I): I4 - I9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gick, N. Jander, H.-P. Bestehorn, R.-P. Kienzle, M. Ferenc, K. Werner, T. Comberg, K. Peitz, D. Zohlnhofer, V. Bassignana, et al. Randomized Evaluation of the Effects of Filter-Based Distal Protection on Myocardial Perfusion and Infarct Size After Primary Percutaneous Catheter Intervention in Myocardial Infarction With and Without ST-Segment Elevation Circulation, September 6, 2005; 112(10): 1462 - 1469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gyongyosi and K. Huber Facilitation of primary PCI with ReoPro: reply Eur. Heart J., August 1, 2005; 26(15): 1564 - 1565. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Lefevre, E. Garcia, B. Reimers, I. Lang, C. di Mario, A. Colombo, F.-J. Neumann, M. V. Chavarri, P. Brunel, E. Grube, et al. X-Sizer for Thrombectomy in Acute Myocardial Infarction Improves ST-Segment Resolution: Results of the X-Sizer in AMI for Negligible Embolization and Optimal ST Resolution (X AMINE ST) Trial J. Am. Coll. Cardiol., July 19, 2005; 46(2): 246 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Huczek, J. Kochman, K. J. Filipiak, G. J. Horszczaruk, M. Grabowski, R. Piatkowski, J. Wilczynska, A. Zielinski, B. Meier, and G. Opolski Mean Platelet Volume on Admission Predicts Impaired Reperfusion and Long-Term Mortality in Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention J. Am. Coll. Cardiol., July 19, 2005; 46(2): 284 - 290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Ray, D. A. Morrow, C. M. Gibson, S. Murphy, E. M. Antman, E. Braunwald, and for the ENTIRE-TIMI 23 Study Group Predictors of the rise in vWF after ST elevation myocardial infarction: implications for treatment strategies and clinical outcome: An ENTIRE-TIMI 23 substudy Eur. Heart J., March 1, 2005; 26(5): 440 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y Ohara, Y Hiasa, T Takahashi, K Yamaguchi, R Ogura, T Ogata, K Yuba, K Kusunoki, S Hosokawa, K Kishi, et al. Relation between the TIMI frame count and the degree of microvascular injury after primary coronary angioplasty in patients with acute anterior myocardial infarction Heart, January 1, 2005; 91(1): 64 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Gibson, R. L. Dumaine, E. V. Gelfand, S. A. Murphy, D. A. Morrow, S. D. Wiviott, R. P. Giugliano, C. P. Cannon, E. M. Antman, E. Braunwald, et al. Association of glomerular filtration rate on presentation with subsequent mortality in non-ST-segment elevation acute coronary syndrome; observations in 13307 patients in five TIMI trials Eur. Heart J., November 2, 2004; 25(22): 1998 - 2005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Gibson, S. A. Murphy, A. J. Kirtane, R. P. Giugliano, C. P. Cannon, E. M. Antman, E. Braunwald, and TIMI Study Group Association of duration of symptoms at presentation with angiographic and clinical outcomes after fibrinolytic therapy in patients with st-segment elevation myocardial infarction J. Am. Coll. Cardiol., September 1, 2004; 44(5): 980 - 987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Chugh, J. Koppel, M. Scott, L. Shewchuk, D. Goodhart, R. Bonan, J.-C. Tardif, S. G. Worthley, C. DiMario, M. J. Curtis, et al. Coronary flow velocity reserve does not correlate with TIMI frame count in patients undergoing non-emergency percutaneous coronary intervention J. Am. Coll. Cardiol., August 18, 2004; 44(4): 778 - 782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Gibson, L. K. Jennings, S. A. Murphy, D. P. Lorenz, R. P. Giugliano, R. A. Harrington, S. Cholera, R. Krishnan, R. M. Califf, E. Braunwald, et al. Association Between Platelet Receptor Occupancy After Eptifibatide (Integrilin) Therapy and Patency, Myocardial Perfusion, and ST-Segment Resolution Among Patients With ST-Segment-Elevation Myocardial Infarction: An INTEGRITI (Integrilin and Tenecteplase in Acute Myocardial Infarction) Substudy Circulation, August 10, 2004; 110(6): 679 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sato, H. Iida, A. Tanaka, H. Tanaka, S. Shimodouzono, E. Uchida, T. Kawarabayashi, and J. Yoshikawa The decrease of plaque volume during percutaneous coronary intervention has a negative impact on coronary flow in acute myocardial infarction: A major role of percutaneous coronary intervention-induced embolization J. Am. Coll. Cardiol., July 21, 2004; 44(2): 300 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Gibson and A. Schomig Coronary and Myocardial Angiography: Angiographic Assessment of Both Epicardial and Myocardial Perfusion Circulation, June 29, 2004; 109(25): 3096 - 3105. [Full Text] [PDF]
|
|
|
|
|
|
C. M. Gibson, J. Karha, S. A. Murphy, J. A. de Lemos, D. A. Morrow, R. P. Giugliano, M. T. Roe, R. A. Harrington, C. P. Cannon, E. M. Antman, et al. Association of a pulsatile blood flow pattern on coronary arteriography and short-term clinical outcomes in acute myocardial infarction J. Am. Coll. Cardiol., April 7, 2004; 43(7): 1170 - 1176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J A de Lemos and J J Warner New tools for assessing microvascular obstruction in patients with ST elevation myocardial infarction Heart, February 1, 2004; 90(2): 119 - 120. [Full Text] [PDF]
|
|
|
|
|
|
C. M. Gibson, D. S. Pinto, S. A. Murphy, D. A. Morrow, H.-P. Hobbach, S. D. Wiviott, R. P. Giugliano, C. P. Cannon, E. M. Antman, E. Braunwald, et al. Association of creatinine and creatinine clearance on presentation in acute myocardial infarction with subsequent mortality J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1535 - 1543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Bonnemeier, U. K.H. Wiegand, J. Friedlbinder, S. Schulenburg, F. Hartmann, F. Bode, H. A. Katus, and G. Richardt Reflex Cardiac Activity in Ischemia and Reperfusion: Heart Rate Turbulence in Patients Undergoing Direct Percutaneous Coronary Intervention for Acute Myocardial Infarction Circulation, August 26, 2003; 108(8): 958 - 964. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Cotter, E. Kaluski, O. Milo, A. Blatt, A. Salah, A. Hendler, R. Krakover, A. Golick, and Z. Vered LINCS: L-NAME (a NO synthase inhibitor) In the treatment of refractory Cardiogenic Shock: A prospective randomized study Eur. Heart J., July 2, 2003; 24(14): 1287 - 1295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D V Cokkinos, A Manginas, and V Voudris Coronary flow: clinical considerations Heart, April 1, 2003; 89(4): 361 - 363. [Full Text] [PDF]
|
|
|
|
|
|
A. Dibra, J. Mehilli, J. Dirschinger, J.u. Pache, J. Neverve, M. Schwaiger, A. Schomig, and A. Kastrati Thrombolysis in myocardial infarction myocardial perfusion grade in angiography correlates with myocardial salvage in patients with acute myocardial infarction treated with stenting or thrombolysis J. Am. Coll. Cardiol., March 19, 2003; 41(6): 925 - 929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kurisu, I. Inoue, T. Kawagoe, M. Ishihara, Y. Shimatani, K. Nishioka, T. Umemura, S. Nakamura, M. Yoshida, and H. Sato Myocardial perfusion and fatty acid metabolism in patients with tako-tsubo-like left ventricular dysfunction J. Am. Coll. Cardiol., March 5, 2003; 41(5): 743 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Haager, P. Christott, N. Heussen, W. Lepper, P. Hanrath, and R. Hoffmann Prediction of clinical outcome after mechanical revascularization in acute myocardial infarction by markers of myocardial reperfusion J. Am. Coll. Cardiol., February 19, 2003; 41(4): 532 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K Greaves, S R Dixon, M Fejka, W W O'Neill, S R Redwood, M S Marber, and R Senior Myocardial contrast echocardiography is superior to other known modalities for assessing myocardial reperfusion after acute myocardial infarction Heart, February 1, 2003; 89(2): 139 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.S Petronio, D Rovai, G Musumeci, R Baglini, C Nardi, U Limbruno, C Palagi, D Volterrani, and M Mariani Effects of abciximab on microvascular integrity and left ventricular functional recovery in patients with acute infarction treated by primary coronary angioplasty Eur. Heart J., January 1, 2003; 24(1): 67 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yamamoto, H. Ito, K. Iwakura, S. Kawano, M. Ikushima, T. Masuyama, T. Ogihara, and K. Fujii Two different coronary blood flow velocity patterns in thrombolysis in myocardial infarction flow grade 2 in acute myocardial infarction: Insight into mechanisms of microvascular dysfunction J. Am. Coll. Cardiol., November 20, 2002; 40(10): 1755 - 1760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.-J. Neumann and N. Jander How to best counteract the enemies? By ensuring adequate oxygen delivery Eur. Heart J. Suppl., November 1, 2002; 4(suppl_G): G35 - G42. [Abstract] [PDF]
|
|
|
|
|
|
D. P. Faxon, R. J. Gibbons, N. A. F. Chronos, P. A. Gurbel, F. Sheehan, and HALT-MI Investigators The effect of blockade of the CD11/CD18 integrin receptor on infarct size in patients with acute myocardial infarction treated with direct angioplasty: the results of the HALT-MI study J. Am. Coll. Cardiol., October 2, 2002; 40(7): 1199 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-i. Kotani, S. Nanto, G. S. Mintz, M. Kitakaze, T. Ohara, T. Morozumi, S. Nagata, and M. Hori Plaque Gruel of Atheromatous Coronary Lesion May Contribute to the No-Reflow Phenomenon in Patients With Acute Coronary Syndrome Circulation, September 24, 2002; 106(13): 1672 - 1677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-K. Wong, J.K. French, M.W. Krucoff, W. Gao, P.E. Aylward, and H.D. White Slowed ST segment recovery despite early infarct artery patency in patients with Q waves at presentation with a first acute myocardial infarction. Implications of initial Q waves on myocyte reperfusion Eur. Heart J., September 2, 2002; 23(18): 1449 - 1455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Beran, I. Lang, W. Schreiber, S. Denk, T. Stefenelli, B. Syeda, G. Maurer, D. Glogar, and P. Siostrzonek Intracoronary Thrombectomy With the X-Sizer Catheter System Improves Epicardial Flow and Accelerates ST-Segment Resolution in Patients With Acute Coronary Syndrome: A Prospective, Randomized, Controlled Study Circulation, May 21, 2002; 105(20): 2355 - 2360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Rezkalla and R. A. Kloner No-Reflow Phenomenon Circulation, February 5, 2002; 105(5): 656 - 662. [Full Text] [PDF]
|
|
|
|
|
|
B. G. Angeja, M. Gunda, S. A. Murphy, B. E. Sobel, A. C. Rundle, M. Syed, A. Asfour, S. Borzak, S. G. Gourlay, H. V. Barron, et al. TIMI Myocardial Perfusion Grade and ST Segment Resolution: Association With Infarct Size as Assessed by Single Photon Emission Computed Tomography Imaging Circulation, January 22, 2002; 105(3): 282 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A APPLEBY, B. G ANGEJA, K. DAUTERMAN, and C M. GIBSON Angiographic assessment of myocardial perfusion: TIMI myocardial perfusion (TMP) grading system Heart, November 1, 2001; 86(5): 485 - 486. [Full Text] [PDF]
|
|
|
|
|
|
S. Hamada, T. Nishiue, S. Nakamura, T. Sugiura, H. Kamihata, H. Miyoshi, Y. Imuro, and T. Iwasaka TIMI frame count immediately after primary coronary angioplasty as a predictor of functional recovery in patients with TIMI 3 reperfused acute myocardial infarction J. Am. Coll. Cardiol., September 1, 2001; 38(3): 666 - 671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Gibson, J. A. de Lemos, S. A. Murphy, S. J. Marble, C. H. McCabe, C. P. Cannon, E. M. Antman, and E. Braunwald Combination Therapy With Abciximab Reduces Angiographically Evident Thrombus in Acute Myocardial Infarction : A TIMI 14 Substudy Circulation, May 29, 2001; 103(21): 2550 - 2554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Roe, E. M. Ohman, A. C. P. Maas, R. H. Christenson, K. W. Mahaffey, C. B. Granger, R. A. Harrington, R. M. Califf, and M. W. Krucoff Shifting the open-artery hypothesis downstream: the quest for optimal reperfusion J. Am. Coll. Cardiol., January 1, 2001; 37(1): 9 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. V. Barron, C. P. Cannon, S. A. Murphy, E. Braunwald, and C. M. Gibson Association Between White Blood Cell Count, Epicardial Blood Flow, Myocardial Perfusion, and Clinical Outcomes in the Setting of Acute Myocardial Infarction : A Thrombolysis In Myocardial Infarction 10 Substudy Circulation, November 7, 2000; 102(19): 2329 - 2334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Bhatt, S. G. Ellis, C. M. Gibson, S. A. Murphy, M. J. Rizzo, K. A. Ryan, S. J. Marble, C. H. McCabe, C. P. Cannon, F. Van de Werf, et al. Is the Corrected TIMI Frame Count an Independent Predictor of Adverse Outcome? Response Circulation, July 11, 2000; 102 (2): e19 - e19. [Full Text] [PDF]
|
|
|
|
|
|
J. K. French, T. A. Hyde, I. T. Straznicky, J. Andrews, M. Lund, D. J. Amos, A. Zambanini, C. J. Ellis, B. J. Webber, S. C. McLaughlin, et al. Relationship between corrected TIMI frame counts at three weeks and late survival after myocardial infarction J. Am. Coll. Cardiol., May 1, 2000; 35(6): 1516 - 1524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Kern Coronary Physiology Revisited : Practical Insights From the Cardiac Catheterization Laboratory Circulation, March 21, 2000; 101(11): 1344 - 1351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Faxon Predicting Restenosis : Bigger Is Better but Not Best Circulation, March 7, 2000; 101(9): 946 - 947. [Full Text] [PDF]
|
|
|
|
|
|
G. Stankovic, A. Manginas, V. Voudris, G. Pavlides, G. Athanassopoulos, M. Ostojic, and D. V. Cokkinos Prediction of Restenosis After Coronary Angioplasty by Use of a New Index : TIMI Frame Count/Minimal Luminal Diameter Ratio Circulation, March 7, 2000; 101(9): 962 - 968. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Gibson, C. P. Cannon, S. A. Murphy, K. A. Ryan, R. Mesley, S. J. Marble, C. H. McCabe, F. Van de Werf, and E. Braunwald Relationship of TIMI Myocardial Perfusion Grade to Mortality After Administration of Thrombolytic Drugs Circulation, January 18, 2000; 101(2): 125 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Gibson, C. P. Cannon, S. A. Murphy, S. J. Marble, H. V. Barron, E. Braunwald, and for the TIMI Study Group Relationship of the TIMI Myocardial Perfusion Grades, Flow Grades, Frame Count, and Percutaneous Coronary Intervention to Long-Term Outcomes After Thrombolytic Administration in Acute Myocardial Infarction Circulation, April 23, 2002; 105(16): 1909 - 1913. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||