(Circulation. 1999;100:14-20.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Relationship Between Delay in Performing Direct Coronary Angioplasty and Early Clinical Outcome in Patients With Acute Myocardial Infarction
Results From the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb) Trial
From the Division of Cardiovascular Diseases, Mayo Clinic (P.B.B., D.R.H.), Rochester, Minn; the Department of Cardiology, Cleveland Clinic (S.G.E., E.J.T.), Cleveland, Ohio; the Division of Cardiology, Duke University (C.B.G., D.A.C., R.M.C.), Durham, NC; and Hospital Clinic 1, Provincial de Barcelona (A.B.), Barcelona, Spain.
Correspondence to Peter B. Berger, MD, Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail berger.peter{at}mayo.edu
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Abstract |
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Background—Time to treatment with thrombolytic therapy is a critical determinant of mortality in acute myocardial infarction. Little is known about the relationship between the time to treatment with direct coronary angioplasty and clinical outcome. The objectives of this study were to determine both the time required to perform direct coronary angioplasty in the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb) trial and its relationship to clinical outcome.
Methods and Results—Patients randomized to direct
coronary angioplasty (n=565) were divided into groups based on
the time between study enrollment and first balloon inflation. Patients
randomized to angioplasty who did not undergo the procedure were also
analyzed. The median time from study enrollment to first
balloon inflation was 76 minutes; 19% of patients assigned to
angioplasty did not undergo an angioplasty procedure. The 30-day
mortality rate of patients who underwent balloon inflation 
60 minutes
after study enrollment was 1.0%; 61 to 75 minutes after enrollment,
3.7%; 76 to 90 minutes after enrollment, 4.0%; and 
91 minutes after
enrollment, 6.4%. The mortality rate of patients assigned to
angioplasty who never underwent the procedure was 14.1%
(P=0.001). Logistic regression analysis revealed
that the time from enrollment to first balloon inflation was a
significant predictor of mortality within 30 days; after adjustment for
differences in baseline characteristics, the odds of death increased
1.6 times (P=0.008) for a movement from each time
interval to the next.
Conclusions—The time to treatment with direct PTCA, as with thrombolytic therapy, is a critical determinant of mortality.
Key Words: reperfusion • myocardial infarction • angioplasty • mortality • survival
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Introduction |
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Thrombolytic therapy has been proven to reduce the mortality of acute myocardial infarction in prospective, randomized, controlled trials involving >60 000 patients.1 The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) trial and its angiographic substudy support the hypothesis that the rapid and complete restoration of blood flow is the mechanism by which thrombolytic therapy reduces early mortality in acute myocardial infarction.2 3 4 5
Some argue that direct coronary angioplasty should be the treatment of choice for acute myocardial infarction because it is believed to achieve reperfusion more rapidly and completely and in more patients than thrombolytic therapy.6 However, the relationship between mortality and the speed with which reperfusion is achieved has not been established with direct angioplasty as it has been with thrombolytic therapy. In addition, many proponents of thrombolytic therapy argue that the rapidity with which reperfusion was achieved and the high reperfusion rates with direct angioplasty in the randomized trials that compared direct angioplasty and thrombolytic therapy primarily at large tertiary-care medical centers may not be representative of the results that can be achieved in community hospitals.7 8 9 10 Indeed, in the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb) trial (the largest international randomized trial to date, comparing thrombolytic therapy with direct coronary angioplasty in 57 hospitals in 9 countries to more accurately reflect the performance of direct coronary angioplasty), direct coronary angioplasty had less of an advantage over thrombolytic therapy than was present in the other randomized trials.11
Little information has been reported from the GUSTO-IIb trial about the time required to perform angioplasty and about the relationship between the time required to perform angioplasty and clinical outcome. It is not known whether angioplasty was performed less rapidly than in the randomized trials performed primarily at major academic centers and whether hospital delay in performing angioplasty was associated with an increased mortality that could have accounted for the lesser benefit associated with angioplasty in GUSTO-IIb.
Therefore, we analyzed data from the GUSTO-IIb trial to determine the time required to perform angioplasty and the relationship between the hospital delay in performing angioplasty and early clinical outcome.
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Methods |
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Study Organization
The GUSTO-IIb Direct PTCA substudy was a prospective substudy of the GUSTO-IIb trial.11 12 Fifty-seven hospitals in 9 countries participated in the substudy comparing direct coronary angioplasty with thrombolytic therapy. To participate, each site was required to perform
200 angioplasty
procedures a year and to have 1 interventionist who performed 50
angioplasties yearly. Eight-five percent of participating sites and
operators performed >400 and 75 angioplasties yearly, respectively. A
24-hour on-call team was mandated, but there was no requirement about
the speed with which angioplasty had to be performed for participation
in the trial. Sites were required to be able to provide operating room
backup if emergency bypass surgery was necessary.
Patient Population
Patients presenting to a participating hospital within 12
hours after symptom onset (chest pain lasting 20 minutes accompanied
by ECG signs of 0.2-mV ST-segment elevation in 2 contiguous leads
or left bundle-branch block) were eligible for enrollment. Exclusion
criteria were identical to those in the main GUSTO-IIb trial. Patients
gave informed consent before study enrollment. The protocol was
approved by the Institutional Review Board at each hospital.
Randomization and Treatment Strategies
Eligible patients (n=1138) were randomized to either primary
PTCA (n=565) or accelerated tissue plasminogen
activator (t-PA; 15-mg intravenous bolus
followed by an infusion of 0.75 mg/kg over 30 minutes, not to exceed 50
mg, and then 0.50 mg/kg over the next 60 minutes, not to exceed 35 mg,
for a total maximum of 100 mg). Patients receiving t-PA (n=573) were
not included in any of the analyses in the present
study.
Primary Angioplasty
Angioplasty was performed with the intent of restoring normal
antegrade blood flow in the infarct artery as soon as possible. The
infarct artery was the only target, except in patients with
hemodynamic deterioration despite restoration of its
patency. For patients with coronary anatomy unfavorable
for angioplasty, including those with left main stenoses or
critical 3-vessel disease, the protocol recommended that bypass surgery
be strongly considered instead of angioplasty. In patients whose
infarct arteries showed Thrombolysis In Myocardial
Infarction (TIMI) grade 3 flow before the angioplasty procedure, the
decision of whether to perform angioplasty was left to the judgment of
the operator.13
Concomitant Therapy
All patients received standard medical care, including
chewable aspirin at the time of enrollment. In the GUSTO-IIb substudy,
patients were assigned in a 2x2 factorial design to either heparin or
hirudin as in the main GUSTO-IIb trial. After coronary
angiography was completed, if it was determined that angioplasty was
indicated, the study thrombin inhibitor was titrated in a
double-blind fashion by 3000-U heparin or 30-mg hirudin increments to
achieve an activated clotting time of 350 seconds. After the
angioplasty procedure, the study drug was temporarily stopped to allow
for early sheath removal. Patients then received a 3- to 5-day infusion
of either heparin or hirudin with adjustment to maintain the
activated partial thromboplastin time in the 60- to 85-second
range. Because there was no difference in the clinical outcome of
angioplasty patients treated with heparin versus hirudin, all
angioplasty patients were analyzed together regardless of which
thrombin inhibitor they received.11 12 Other
cardiac medications were administered at the discretion of the
physician. Similarly, the use of intra-aortic balloon counterpulsation,
functional (stress) testing, delayed angiography, angioplasty, and
bypass surgery was left to the investigator.
Time to Angioplasty
Patients randomized to angioplasty (n=565) were divided into
groups based on the time between their enrollment in the study and the
first angioplasty balloon inflation. These groups included patients in
whom this time interval was 60 minutes (n=104), 61 to 75 minutes
(n=109), 76 to 90 minutes (n=76), and >90 minutes (n=140). A fifth
group of patients randomized to balloon angioplasty who never underwent
the procedure was also analyzed (n=93). These time
intervals were chosen because they permit comparison with patency rates
after thrombolytic therapy, which are usually
analyzed at 60 and 90 minutes.
Of the 93 patients in whom angioplasty was not performed, 5 died within 2 hours, before angioplasty could be performed. Six had left main disease >50% and were referred for bypass surgery. Ten others had severe multivessel disease and were also referred for bypass surgery. Three patients underwent immediate bypass surgery for anatomic reasons related to the infarct artery. One patient had severe mitral regurgitation requiring surgery. In 36 patients, the infarct artery was <70% stenotic, there was TIMI 3 flow, or both. In the remaining 32 patients, the exact reasons that PTCA was not performed remain unknown.
Patients in whom either the time of enrollment or the time of balloon
angioplasty was not available (n=43, 8%) were excluded from
this analysis. To determine whether bias was present in the
ascertainment of these data, we compared the baseline characteristics
and clinical outcome of patients in whom these time data were and were
not available. There were no significant differences in any of the
baseline characteristics included in Table 1
or in 30-day mortality between
patients in whom these time data were and were not available.
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Statistical Analyses
Prespecified baseline variables were compared among
the analysis subgroups by use of a 
2
test for categorical variables and Wilcoxon rank sum test
for continuous variables. Logistic regression models were used to
assess the relationship between the analysis subgroups and the
outcomes of interest while controlling for certain baseline
characteristics. Baseline variables used in the analysis
were as follows: age, weight, height, race, sex, family history of
coronary heart disease, hypertension, diabetes,
peripheral vascular disease,
hypercholesterolemia, smoking status (current
smoker, history of smoking, or nonsmoker), previous angina, previous
infarction, previous cerebrovascular disease, prior PTCA, prior CABG,
blood pressure, heart rate, baseline Killip class, and minutes from
symptom onset to enrollment. Because a large number of comparisons were
performed, a probability value of 0.05 was not considered to
represent a significant difference between variables. Only
probability values 0.005 were considered significant. In the logistic
regression model, values of <0.05 were considered significant. All
analyses were performed with SAS software.14
The primary end point of this study was all-cause mortality within 30 days. To find the best possible predictor of the 30-day death end point, the time from study enrollment to first balloon inflation was modeled as a continuous, categorical, and ordinal variable. The best relationship was achieved when the time from enrollment to first balloon inflation was analyzed in categories (chosen to allow comparison with previously reported patency rates with thrombolytic therapy, as described above) that roughly represented quartiles of the study population based on time to inflation; these categories were assigned values from 1 to 5. The time-to-inflation variable was then treated as a 1-degree-of-freedom linear variable in the analysis. The logistic model assessing the relationship between 30-day death and category of time from study enrollment to first balloon inflation was partially adjusted for the baseline variables of age, systolic blood pressure, baseline Killip class (I to II or III to IV), smoking status (noncurrent smoker versus current smoker), and diagnosis or treatment of cancer in the last 5 years. Owing to the small sample size and low event rate, complete adjustment for other baseline variables was not performed. This model appears adequate, however, because the time effect remained consistent as each new adjusting factor was added to the model.
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Results |
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Baseline Characteristics
The baseline characteristics of patients in GUSTO-IIb randomized to angioplasty are revealed in Table 1
. There were few
differences between patients in whom the time between enrollment and
the first balloon inflation was 60 minutes, 61 to 75 minutes, 76 to
90 minutes, or >90 minutes, and patients randomized to balloon
angioplasty who never underwent the procedure. Patients in whom there
was greater delay in performing angioplasty had more severe heart
failure at the time of enrollment, although few patients in the study
(5.1%) had baseline Killip class III or IV heart failure. The median
time from study enrollment to reperfusion was 76 minutes (25th and 75th
percentiles were 61 and 95 minutes, respectively).
Angiographic Characteristics and Left Ventricular
Ejection Fraction
Multivessel disease (defined as a diameter stenosis 70%
in at least 2 of the 3 major coronary arteries or their major
branches, or a left main stenosis 50%) was present in 26
patients (25%) treated <60 minutes after study enrollment, 43 (40%)
treated 61 to 75 minutes after enrollment, 23 (31%) treated 76 to 90
minutes after enrollment, and 53 patients (38%) treated >91 minutes
after study enrollment. Multivessel disease was present in 30
patients (39%) who underwent angiography but did not undergo
angioplasty (P=0.13).
Ventriculography performed before the angioplasty procedure in 309 patients revealed that the median left ventricular ejection was 60% (with 25th and 75th percentiles of 50% and 67%, respectively) for patients treated within 1 hour of study enrollment, greater than the median ejection fraction of 50% in patients treated 61 to 75 minutes after enrollment (45%, 58%), 51% in patients treated 76 to 90 minutes after enrollment (43%, 60%), and 50% in patients treated >91 minutes after study enrollment (40%, 59%). Patients who did not undergo angioplasty had a mean ejection fraction of 50% (40%, 62%) as well.
Correlates of Delay
We examined the baseline clinical characteristics in Table 1, the frequency of multivessel disease, and 3 characteristics
on the qualifying ECG (infarction site, total amount of ST-segment
elevation, and total amount of ST-segment shift, including both
ST-segment elevation and depression) in an attempt to identify clinical
and ECG correlates of hospital delay in performing direct
coronary angioplasty. None of these characteristics were
associated with greater or lesser delay in performing the angioplasty
procedure. There was also no apparent relationship between time to
treatment and whether heparin or hirudin was used or the annual
angioplasty caseload (625 cases per year at 30 medical centers versus
>625 cases per year at 27 medical centers), although these subset
analyses were underpowered to detect significant
differences.
Clinical Outcome
There were differences in clinical outcome between the different
groups of patients (Figure). Mortality
within 30 days of enrollment was lowest in patients treated within 60
minutes of enrollment and progressively higher among patients with
greater delay between enrollment and first balloon inflation
(P=0.001). Mortality was highest among patients in whom
angioplasty was not performed. A relationship between mortality and
time to angioplasty was still evident after patients in whom
angioplasty was not performed were excluded (P=0.035).
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Among the 73% of patients in whom TIMI 3 flow was ultimately achieved, the mortality rate was 1.5%, whereas it was 11.7% in the 27% of patients who achieved TIMI 0, 1, or 2 flow.
The median time to death, with 25th and 75th percentiles in parentheses, was 0 days (0, 0) for patients treated within 60 minutes, 5 days (0.5, 11.5) for patients treated 61 to 75 minutes after enrollment, 7 days (4, 17) for patients treated 76 to 90 minutes after enrollment, 1 day (1, 4) for patients treated >91 minutes after enrollment, and 0 days (0, 2) for patients assigned to angioplasty who did not undergo an angioplasty procedure.
Multivariate Analysis
Logistic regression analysis was performed to
further evaluate the relationship between time to first inflation and
30-day mortality. After adjustment for age, systolic blood
pressure, baseline Killip class, smoking status, and diagnosis or
treatment of cancer in the last 5 years, the time from enrollment to
first balloon inflation was a significant predictor of 30-day death
(P=0.008). Each time interval was associated with a 1.6
times (95% CI, 1.13 to 2.26; P=0.008) greater risk of death
than the interval preceding it (eg, <60 minutes to 61 to 75 minutes).
This increase in the odds of death associated with delay was roughly
equivalent to a 7-year increment in age (OR, 1.56; 95% CI, 1.16 to
2.11; P=0.004). Inclusion of initial TIMI flow grade had no
detectable impact on the relationship between time to reperfusion and
mortality.
Symptom Onset of Angioplasty
We also analyzed the time from symptom onset to
angioplasty. The data do not demonstrate as strong a relationship
between mortality and time from symptom onset to angioplasty as is
evident in the relationship between mortality and the time from study
enrollment to angioplasty. The mortality of patients with a duration of
symptoms <90 minutes until angioplasty was performed was 0% (n=4);
for patients with symptoms for 91 to 120 minutes until angioplasty,
6.7% (n=14); for those with symptoms for 121 to 180 minutes until
angioplasty, 1.1% (n=87); for patients with symptoms for 181 to 240
minutes, 3.5% (n=116); for those with symptoms for 241 to 300 minutes,
6.9% (n=71); and for patients with symptoms for >300 minutes until
angioplasty, 4.9% (n=117). Among patients in whom angioplasty was not
performed, the mortality rate was 14.1% (n=93).
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Discussion |
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The most important finding of this study is that in patients with acute myocardial infarction who were randomized to direct coronary angioplasty, hospital delay in performing the angioplasty procedure appeared to be associated with an increase in 30-day mortality. The time to angioplasty in the GUSTO-IIb study was longer than in some of the randomized trials, which may have contributed to the lesser benefit seen with direct angioplasty in this study than in other randomized trials comparing direct coronary angioplasty with thrombolytic therapy.
GUSTO-IIb
Several differences between GUSTO-IIb and the other randomized
comparisons of direct coronary angioplasty and
thrombolytic therapy are worth emphasizing. GUSTO-IIb
used accelerated t-PA, the thrombolytic regimen
demonstrated to have the lowest mortality in clinical
trials.3 Most of the other randomized studies used
thrombolytic regimens that achieve lower 90-minute
patency rates; patency rates with thrombolytic therapy
have been shown to correlate with early 30-day
mortality.3 4 In addition, the time from enrollment in the
study to the administration of thrombolytic therapy was
more rapid in GUSTO-IIb than in most of the randomized trials, which
also may have contributed to a lower mortality in the group receiving
thrombolytic therapy.11 15 16 Furthermore,
the time to angioplasty in several of the randomized trials was more
rapid than in GUSTO-IIb (Table 2),
although it must be emphasized that GUSTO-IIb deliberately included a
wide variety of hospitals to better reflect practice patterns
throughout the world.16 17 18 19 20 The time required to perform
angioplasty in GUSTO-IIb might most appropriately be compared with the
time required to perform angioplasty in the more
representative second National Registry of Myocardial
Infarction.8 In this registry of 3648 patients
treated with direct coronary angioplasty at 421 hospitals in
the United States, the median time from hospital
presentation to angioplasty was 2 hours, longer than the
median time from enrollment to treatment of 76 minutes in GUSTO-IIb,
despite not having to take additional time to obtain informed consent,
as required in GUSTO-IIb.
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Duration of Symptoms Before Angioplasty
Our analysis of the relationship between mortality and the
duration of symptoms until angioplasty revealed a weaker association
than was seen with the relationship between mortality and time from
hospital arrival until angioplasty. The duration of a patient's
symptoms is inherently subjective, and patients may not report their
symptom duration accurately. Furthermore, infarct arteries often open
and close in the course of an infarction, which might make the
relationship between symptom duration and outcome less strong. It also
may be that patients who are sicker in some ways come to the hospital
more rapidly than less sick patients, which would introduce bias into
the analysis. Although we strongly support public health
efforts to reduce delay between symptoms of infarction and
presentation to the hospital, the component of delay that
is directly under physicians' control is the delay in achieving
reperfusion after patients present to the hospital. It is this
important component of delay that we primarily addressed in this
study.
Comparison of Patency Rates With Direct Coronary
Angioplasty and Thrombolytic Therapy
A single study has compared the time required to achieve
reperfusion with coronary angioplasty versus
thrombolytic therapy.20 Such comparisons
are fraught with difficulty for many reasons. First, the definition of
success differs between the 2 treatments. Successful angioplasty
usually requires a residual stenosis of <50%; no such
criterion exists for thrombolytic therapy, and in fact,
most patients in whom patency is restored with
thrombolytic therapy have a residual stenosis
>60%. Second, normal antegrade flow (TIMI grade 3 flow) has usually
been required for angioplasty to be considered successful, whereas
traditionally TIMI grade 2 or 3 flow has been required for
thrombolysis to be considered a success. Lastly, the
time required to transport patients to the
catheterization laboratory has been included in
analyses of the time required to achieve reperfusion with
direct coronary angioplasty, whereas the time required to
administer thrombolytic therapy has not been included
in the analyses of patency rates with
thrombolysis. When one accounts for the time to perform
direct coronary angioplasty as well as the time to administer
thrombolytic therapy, patency rates are considerably
higher with direct coronary angioplasty.20 In the
current study, if one includes the mean of 20 minutes from
randomization required to administer t-PA in the
thrombolytic arm of GUSTO-IIb and assumes that the 54%
patency rate with t-PA in GUSTO-I was achieved in the present study
as well, it can be estimated that 54% of patients had normal TIMI 3
flow 110 minutes (20 plus 90 minutes) after study enrollment. In
contrast, 72% of the angioplasty patients (373 of 521 patients with
available time-to-treatment data) in the GUSTO-IIb substudy received
their first balloon inflation within 110 minutes of randomization. The
more rapid achievement of patency with direct coronary
angioplasty provides the most logical explanation of the improved
outcome seen with direct coronary angioplasty in this and other
studies.
Limitations
Although GUSTO-IIb is the largest randomized trial to date
comparing direct coronary angioplasty and
thrombolytic therapy in the treatment of acute
myocardial infarction, the study was nonetheless relatively small;
there were only 30 deaths within 30 days of enrollment among the 522
angioplasty patients with time-to-treatment data. Therefore, the study
was limited in its ability to detect significant correlates of adverse
events while controlling for other variables. The improved clinical
outcome with more rapid reperfusion is consistent with studies
of thousands of patients treated with thrombolytic
therapy in which the time to reperfusion has been conclusively shown to
be a critical determinant of outcome. There is no reason to believe
that timely reperfusion achieved in the catheterization
laboratory is any less important than that achieved with
thrombolysis. In fact, more timely and complete
reperfusion with direct coronary angioplasty is believed to be
the basis of the improved outcome with coronary angioplasty
compared with thrombolytic therapy.
Previous studies have used the time at which the first balloon inflation was performed as a surrogate for the time at which reperfusion was achieved, although admittedly some patients require multiple inflations to achieve reperfusion.19 In GUSTO-IIb, the time at which normal antegrade flow was established was not recorded. However, it is unlikely that the use of the time to first balloon inflation introduced bias into the study or influenced the results indicating that hospital delay was associated with a higher early mortality.
Conclusions
Hospital delay in achieving reperfusion with coronary
angioplasty in acute myocardial infarction increases mortality, as does
delay with thrombolytic therapy. Hospital delay in
performing angioplasty should be eliminated, and the time required to
perform direct angioplasty should be considered when deciding whether
thrombolytic therapy or direct coronary
angioplasty should be administered to patients with acute myocardial
infarction.
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Acknowledgments |
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The authors gratefully acknowledge Penny Hodgson for her invaluable editorial contributions.
Received February 8, 1999; revision received April 8, 1999; accepted April 15, 1999.
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G. W. Stone Angioplasty Strategies in ST-Segment-Elevation Myocardial Infarction: Part I: Primary Percutaneous Coronary Intervention Circulation, July 29, 2008; 118(5): 538 - 551. [Full Text] [PDF]
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H. M. Krumholz, E. H. Bradley, B. K. Nallamothu, H. H. Ting, W. B. Batchelor, E. Kline-Rogers, A. F. Stern, J. R. Byrd, and J. E. Brush Jr A campaign to improve the timeliness of primary percutaneous coronary intervention: Door-to-Balloon: An Alliance for Quality. J. Am. Coll. Cardiol. Intv., February 1, 2008; 1(1): 97 - 104. [Abstract] [Full Text] [PDF]
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B. K. Nallamothu, E. H. Bradley, and H. M. Krumholz Time to Treatment in Primary Percutaneous Coronary Intervention N. Engl. J. Med., October 18, 2007; 357(16): 1631 - 1638. [Full Text] [PDF]
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W. E. Boden, K. Eagle, and C. B. Granger Reperfusion Strategies in Acute ST-Segment Elevation Myocardial Infarction: A Comprehensive Review of Contemporary Management Options J. Am. Coll. Cardiol., September 4, 2007; 50(10): 917 - 929. [Abstract] [Full Text] [PDF]
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V. N. Dhruva, S. I. Abdelhadi, A. Anis, W. Gluckman, D. Hom, W. Dougan, E. Kaluski, B. Haider, and M. Klapholz ST-Segment Analysis Using Wireless Technology in Acute Myocardial Infarction (STAT-MI) Trial J. Am. Coll. Cardiol., August 7, 2007; 50(6): 509 - 513. [Abstract] [Full Text] [PDF]
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U. N. Khot, M. L. Johnson, C. Ramsey, M. B. Khot, R. Todd, S. R. Shaikh, and W. J. Berg Emergency Department Physician Activation of the Catheterization Laboratory and Immediate Transfer to an Immediately Available Catheterization Laboratory Reduce Door-to-Balloon Time in ST-Elevation Myocardial Infarction Circulation, July 3, 2007; 116(1): 67 - 76. [Abstract] [Full Text] [PDF]
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A. Lerman, D. R. Holmes, J. Herrmann, and B. J. Gersh Microcirculatory dysfunction in ST-elevation myocardial infarction: cause, consequence, or both? Eur. Heart J., April 1, 2007; 28(7): 788 - 797. [Abstract] [Full Text] [PDF]
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M. Moscucci and K. A. Eagle Reducing the Door-to-Balloon Time for Myocardial Infarction with ST-Segment Elevation N. Engl. J. Med., November 30, 2006; 355(22): 2364 - 2365. [Full Text] [PDF]
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E. H. Bradley, J. Herrin, Y. Wang, B. A. Barton, T. R. Webster, J. A. Mattera, S. A. Roumanis, J. P. Curtis, B. K. Nallamothu, D. J. Magid, et al. Strategies for Reducing the Door-to-Balloon Time in Acute Myocardial Infarction N. Engl. J. Med., November 30, 2006; 355(22): 2308 - 2320. [Abstract] [Full Text] [PDF]
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D. K. Moser, L. P. Kimble, M. J. Alberts, A. Alonzo, J. B. Croft, K. Dracup, K. R. Evenson, A. S. Go, M. M. Hand, R. U. Kothari, et al. Reducing Delay in Seeking Treatment by Patients With Acute Coronary Syndrome and Stroke: A Scientific Statement From the American Heart Association Council on Cardiovascular Nursing and Stroke Council Circulation, July 11, 2006; 114(2): 168 - 182. [Abstract] [Full Text] [PDF]
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R. L. McNamara, Y. Wang, J. Herrin, J. P. Curtis, E. H. Bradley, D. J. Magid, E. D. Peterson, M. Blaney, P. D. Frederick, H. M. Krumholz, et al. Effect of Door-to-Balloon Time on Mortality in Patients With ST-Segment Elevation Myocardial Infarction J. Am. Coll. Cardiol., June 6, 2006; 47(11): 2180 - 2186. [Abstract] [Full Text] [PDF]
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T. D. Henry, J. M. Atkins, M. S. Cunningham, G. S. Francis, W. J. Groh, R. A. Hong, K. B. Kern, D. M. Larson, E. M. Ohman, J. P. Ornato, et al. ST-Segment Elevation Myocardial Infarction: Recommendations on Triage of Patients to Heart Attack Centers: Is it Time for a National Policy for the Treatment of ST-Segment Elevation Myocardial Infarction? J. Am. Coll. Cardiol., April 4, 2006; 47(7): 1339 - 1345. [Abstract] [Full Text] [PDF]
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M. Moscucci and K. A. Eagle Door-to-Balloon Time in Primary Percutaneous Coronary Intervention: Is the 90-Minute Gold Standard an Unreachable Chimera? Circulation, February 28, 2006; 113(8): 1048 - 1050. [Full Text] [PDF]
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B. R. Brodie, C. Hansen, T. D. Stuckey, S. Richter, D. S. VerSteeg, N. Gupta, W. E. Downey, and M. Pulsipher Door-to-Balloon Time With Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction Impacts Late Cardiac Mortality in High-Risk Patients and Patients Presenting Early After the Onset of Symptoms J. Am. Coll. Cardiol., January 17, 2006; 47(2): 289 - 295. [Abstract] [Full Text] [PDF]
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R. L. McNamara, J. Herrin, E. H. Bradley, E. L. Portnay, J. P. Curtis, Y. Wang, D. J. Magid, M. Blaney, H. M. Krumholz, and for the NRMI Investigators Hospital Improvement in Time to Reperfusion in Patients With Acute Myocardial Infarction, 1999 to 2002 J. Am. Coll. Cardiol., January 3, 2006; 47(1): 45 - 51. [Abstract] [Full Text] [PDF]
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S. C. Smith Jr, T. E. Feldman, J. W. Hirshfeld Jr, A. K. Jacobs, M. J. Kern, S. B. King III, D. A. Morrison, W. W. O'Neill, H. V. Schaff, P. L. Whitlow, et al. ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention) J. Am. Coll. Cardiol., January 3, 2006; 47(1): 216 - 235. [Full Text] [PDF]
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S. C. Smith Jr, T. E. Feldman, J. W. Hirshfeld Jr, A. K. Jacobs, M. J. Kern, S. B. King III, D. A. Morrison, W. W. O'Neill, H. V. Schaff, P. L. Whitlow, et al. ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention) Circulation, January 3, 2006; 113(1): 156 - 175. [Full Text] [PDF]
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Part 8: Stabilization of the Patient With Acute Coronary Syndromes Circulation, December 13, 2005; 112(24_suppl): IV-89 - IV-110. [Full Text] [PDF]
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T. P. Wharton Jr, E. C. Keeley, C. L. Grines, T. P. Wharton Jr, E. C. Keeley, and C. L. Grines The Case for Community Hospital Angioplasty Circulation, November 29, 2005; 112(22): 3509 - 3534. [Full Text] [PDF]
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Part 5: Acute Coronary Syndromes Circulation, November 29, 2005; 112(22_suppl): III-55 - III-72. [Full Text] [PDF]
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E. H. Bradley, S. A. Roumanis, M. J. Radford, T. R. Webster, R. L. McNamara, J. A. Mattera, B. A. Barton, D. N. Berg, E. L. Portnay, H. Moscovitz, et al. Achieving Door-to-Balloon Times That Meet Quality Guidelines: How Do Successful Hospitals Do It? J. Am. Coll. Cardiol., October 4, 2005; 46(7): 1236 - 1241. [Abstract] [Full Text] [PDF]
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K. Huber, R. D. Caterina, S. D. Kristensen, F. W.A. Verheugt, G. Montalescot, L. B. Maestro, F. V. d. Werf, and for the Task Force on Pre-hospital Reperfusion The Pre-hospital reperfusion therapy: a strategy to improve therapeutic outcome in patients with ST-elevation myocardial infarction Eur. Heart J., October 1, 2005; 26(19): 2063 - 2074. [Full Text] [PDF]
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P G Steg and J-M Juliard Primary percutaneous coronary intervention in acute myocardial infarction: time, time, and time! Heart, August 1, 2005; 91(8): 993 - 994. [Abstract] [Full Text] [PDF]
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A. J. Lansky, C. Pietras, R. A. Costa, Y. Tsuchiya, B. R. Brodie, D. A. Cox, E. D. Aymong, T. D. Stuckey, E. Garcia, J. E. Tcheng, et al. Gender Differences in Outcomes After Primary Angioplasty Versus Primary Stenting With and Without Abciximab for Acute Myocardial Infarction: Results of the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Trial Circulation, April 5, 2005; 111(13): 1611 - 1618. [Abstract] [Full Text] [PDF]
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B. J. Gersh, G. W. Stone, H. D. White, and D. R. Holmes Jr Pharmacological Facilitation of Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction: Is the Slope of the Curve the Shape of the Future? JAMA, February 23, 2005; 293(8): 979 - 986. [Abstract] [Full Text] [PDF]
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H. C. Herrmann Transfer for Primary Angioplasty: The Importance of Time Circulation, February 15, 2005; 111(6): 718 - 720. [Full Text] [PDF]
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B. K. Nallamothu, E. R. Bates, J. Herrin, Y. Wang, E. H. Bradley, H. M. Krumholz, and for the NRMI Investigators Times to Treatment in Transfer Patients Undergoing Primary Percutaneous Coronary Intervention in the United States: National Registry of Myocardial Infarction (NRMI)-3/4 Analysis Circulation, February 15, 2005; 111(6): 761 - 767. [Abstract] [Full Text] [PDF]
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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]
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Writing Committee Members, E. M. Antman, D. T. Anbe, P. W. Armstrong, E. R. Bates, L. A. Green, M. Hand, J. S. Hochman, H. M. Krumholz, F. G. Kushner, et al. ACC/AHA guidelines for the management of patients with ST-Elevation myocardial infarction--executive summary: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (writing committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction) J. Am. Coll. Cardiol., August 4, 2004; 44(3): 671 - 719. [Full Text] [PDF]
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E. M. Antman, D. T. Anbe, P. W. Armstrong, E. R. Bates, L. A. Green, M. Hand, J. S. Hochman, H. M. Krumholz, F. G. Kushner, G. A. Lamas, et al. ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction--Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction) Circulation, August 3, 2004; 110(5): 588 - 636. [Full Text] [PDF]
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G. De Luca, A. W.J van't Hof, M.-J. de Boer, J. P. Ottervanger, J. C.A Hoorntje, A.T.M. Gosselink, J.-H. E Dambrink, F. Zijlstra, and H. Suryapranata Time-to-treatment significantly affects the extent of ST-segment resolution and myocardial blush in patients with acute myocardial infarction treated by primary angioplasty Eur. Heart J., June 2, 2004; 25(12): 1009 - 1013. [Abstract] [Full Text] [PDF]
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A. M. Lincoff Coupling Drug and Catheter Therapy for Myocardial Infarction JAMA, February 25, 2004; 291(8): 1000 - 1002. [Full Text] [PDF]
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R. P. Giugliano and E. Braunwald Selecting the Best Reperfusion Strategy in ST-Elevation Myocardial Infarction: It's All a Matter of Time Circulation, December 9, 2003; 108(23): 2828 - 2830. [Full Text] [PDF]
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P. G. Steg, E. Bonnefoy, S. Chabaud, F. Lapostolle, P.-Y. Dubien, P. Cristofini, A. Leizorovicz, P. Touboul, and for the Comparison of Angioplasty and Prehospital Impact of Time to Treatment on Mortality After Prehospital Fibrinolysis or Primary Angioplasty: Data From the CAPTIM Randomized Clinical Trial Circulation, December 9, 2003; 108(23): 2851 - 2856. [Abstract] [Full Text] [PDF]
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W. D. Weaver All Hospitals Are Not Equal for Treatment of Patients With Acute Myocardial Infarction Circulation, October 14, 2003; 108(15): 1768 - 1771. [Full Text] [PDF]
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G. De Luca, H. Suryapranata, F. Zijlstra, A. W. J. van't Hof, J. C. A. Hoorntje, A. T. M. Gosselink, J.-H. Dambrink, M.-J. de Boer, and ZWOLLE Myocardial Infarction Study Group Symptom-onset-to-balloon time and mortality in patients with acute myocardial infarction treated by primary angioplasty J. Am. Coll. Cardiol., September 17, 2003; 42(6): 991 - 997. [Abstract] [Full Text] [PDF]
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A. Schomig, G. Ndrepepa, J. Mehilli, M. Schwaiger, H. Schuhlen, S. Nekolla, J. Pache, S. Martinoff, H. Bollwein, and A. Kastrati Therapy-Dependent Influence of Time-to-Treatment Interval on Myocardial Salvage in Patients With Acute Myocardial Infarction Treated With Coronary Artery Stenting or Thrombolysis Circulation, September 2, 2003; 108(9): 1084 - 1088. [Abstract] [Full Text] [PDF]
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H. L. Dauerman and B. E. Sobel Synergistic treatment of ST-segmentelevation myocardial infarction with pharmacoinvasive recanalization J. Am. Coll. Cardiol., August 20, 2003; 42(4): 646 - 651. [Abstract] [Full Text] [PDF]
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K. Iwakura, H. Ito, S. Kawano, A. Okamura, K. Asano, T. Kuroda, K. Tanaka, T. Masuyama, M. Hori, and K. Fujii Detection of TIMI-3 Flow Before Mechanical Reperfusion With Ultrasonic Tissue Characterization in Patients With Anterior Wall Acute Myocardial Infarction Circulation, July 1, 2003; 107(25): 3159 - 3164. [Abstract] [Full Text] [PDF]
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E. J. Topol and D. J. Kereiakes Regionalization of Care for Acute Ischemic Heart Disease: A Call for Specialized Centers Circulation, March 25, 2003; 107(11): 1463 - 1466. [Full Text] [PDF]
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D. J. Moliterno and A. W. Chan Glycoprotein IIb/IIIa inhibition in early intent-to-stent treatment of acute coronary syndromes: EPISTENT, ADMIRAL, CADILLAC, and TARGET J. Am. Coll. Cardiol., February 19, 2003; 41(4_Suppl_S): 49S - 54S. [Abstract] [Full Text] [PDF]
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R. H. Mehta, D. A. Criger, C. B. Granger, K. K. Pieper, R. M. Califf, E. J. Topol, and E. R. Bates Patient outcomes after fibrinolytic therapy for acute myocardial infarction at hospitals with and without coronary revascularization capability J. Am. Coll. Cardiol., September 18, 2002; 40(6): 1034 - 1040. [Abstract] [Full Text] [PDF]
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M. Singh, H. H. Ting, P. B. Berger, K. N. Garratt, D. R. Holmes Jr, and B. J. Gersh Rationale for on-site cardiac surgery for primary angioplasty: a time for reappraisal J. Am. Coll. Cardiol., June 19, 2002; 39(12): 1881 - 1889. [Abstract] [Full Text] [PDF]
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D. R. Thiemann Primary angioplasty for elderly patients with myocardial infarction: Theory, practice and possibilities J. Am. Coll. Cardiol., June 5, 2002; 39(11): 1729 - 1732. [Full Text] [PDF]
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D. Faxon and C. Lenfant Timing Is Everything: Motivating Patients to Call 9-1-1 at Onset of Acute Myocardial Infarction Circulation, September 11, 2001; 104(11): 1210 - 1211. [Full Text] [PDF]
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G. W. Stone, D. Cox, E. Garcia, B. R. Brodie, M.-C. Morice, J. Griffin, L. Mattos, A. J. Lansky, W. W. O'Neill, and C. L. Grines Normal Flow (TIMI-3) Before Mechanical Reperfusion Therapy Is an Independent Determinant of Survival in Acute Myocardial Infarction: Analysis From the Primary Angioplasty in Myocardial Infarction Trials Circulation, August 7, 2001; 104(6): 636 - 641. [Abstract] [Full Text] [PDF]
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H. Hashimoto, K. Kitagawa, H. Hougaku, Y. Shimizu, M. Sakaguchi, Y. Nagai, S. Iyama, H. Yamanishi, M. Matsumoto, and M. Hori C-Reactive Protein Is an Independent Predictor of the Rate of Increase in Early Carotid Atherosclerosis Circulation, July 3, 2001; 104(1): 63 - 67. [Abstract] [Full Text] [PDF]
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G. Montalescot, P. Barragan, O. Wittenberg, P. Ecollan, S. Elhadad, P. Villain, J.-M. Boulenc, M.-C. Morice, L. Maillard, M. Pansieri, et al. Platelet Glycoprotein IIb/IIIa Inhibition with Coronary Stenting for Acute Myocardial Infarction N. Engl. J. Med., June 21, 2001; 344(25): 1895 - 1903. [Abstract] [Full Text] [PDF]
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P. W. Armstrong and D. Collen Fibrinolysis for Acute Myocardial Infarction : Current Status and New Horizons for Pharmacological Reperfusion, Part 2 Circulation, June 19, 2001; 103(24): 2987 - 2992. [Full Text] [PDF]
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B. M. R. Spiegel, N. B. Vakil, and J. J. Ofman Endoscopy for Acute Nonvariceal Upper Gastrointestinal Tract Hemorrhage: Is Sooner Better?: A Systematic Review Arch Intern Med, June 11, 2001; 161(11): 1393 - 1404. [Abstract] [Full Text] [PDF]
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R. Zahn, R. Schiele, S. Schneider, A. K. Gitt, H. Wienbergen, K. Seidl, T. Voigtlander, M. Gottwik, G. Berg, E. Altmann, et al. Primary angioplasty versus intravenous thrombolysis in acute myocardial infarction: can we define subgroups of patients benefiting most from primary angioplasty?: Results from the pooled data of the maximal individual therapy in acute myocardial infarction registry and the myocardial infarction registry J. Am. Coll. Cardiol., June 1, 2001; 37(7): 1827 - 1835. [Abstract] [Full Text] [PDF]
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P. Widimsky Pharmacological versus catheter-based reperfusion: What is present state of the art? Eur. Heart J. Suppl., June 1, 2001; 3(suppl_C): C47 - C54. [Abstract] [PDF]
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P.B. Berger and B.J. Gersh Ventricular function after primary angioplasty for acute myocardial infarction: correlates and caveats Eur. Heart J., May 1, 2001; 22(9): 726 - 728. [PDF]
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R. Zahn, R. Schiele, S. Schneider, A. K. Gitt, H. Wienbergen, K. Seidl, C. Bossaller, H. J. Buttner, M. Gottwik, E. Altmann, et al. Decreasing hospital mortality between 1994 and 1998 in patients with acute myocardial infarction treated with primary angioplasty but not in patients treated with intravenous thrombolysis: Results from the pooled data of the maximal individual therapy in acute myocardial infarction (MITRA) registry and the myocardial infarction registry (MIR) J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2064 - 2071. [Abstract] [Full Text] [PDF]
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S. Ojio, H. Takatsu, T. Tanaka, K. Ueno, K. Yokoya, T. Matsubara, T. Suzuki, S. Watanabe, N. Morita, M. Kawasaki, et al. Considerable Time From the Onset of Plaque Rupture and/or Thrombi Until the Onset of Acute Myocardial Infarction in Humans : Coronary Angiographic Findings Within 1 Week Before the Onset of Infarction Circulation, October 24, 2000; 102(17): 2063 - 2069. [Abstract] [Full Text] [PDF]
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B. R. Brodie, G. Kissling, P. B. Berger, D. A. Criger, D. R. Holmes Jr, S. G. Ellis, C. B. Granger, A. Betriu, E. J. Topol, and R. M. Califf Relationship Between Delay in Performing Direct Coronary Angioplasty and Early Clinical Outcome in Patients With Acute Myocardial Infarction Response Circulation, July 25, 2000; 102 (4): e29 - e30. [Full Text] [PDF]
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C. P. Cannon, C. M. Gibson, C. T. Lambrew, D. A. Shoultz, D. Levy, W. J. French, J. M. Gore, W. D. Weaver, W. J. Rogers, and A. J. Tiefenbrunn Relationship of Symptom-Onset-to-Balloon Time and Door-to-Balloon Time With Mortality in Patients Undergoing Angioplasty for Acute Myocardial Infarction JAMA, June 14, 2000; 283(22): 2941 - 2947. [Abstract] [Full Text] [PDF]
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P. B. Berger, N. Danchin, L. Vaur, N. Genes, S. Etienne, M. Angioi, J. Ferrieres, and J.-P. Cambou Treatment of Acute Myocardial Infarction by Primary Coronary Angioplasty or Intravenous Thrombolysis Response Circulation, May 30, 2000; 101 (21): e211 - e212. [Full Text] [PDF]
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D. Thiemann, A. K. Berger, K. A. Schulman, B. J. Gersh, and N. R. Every Primary Angioplasty vs Thrombolysis in Elderly Patients JAMA, February 2, 2000; 283(5): 601 - 602. [Full Text] [PDF]
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