Search PubMed⌕ Search

Biomedical subjects

C M Gibson

Publications and source records attributed to C M Gibson.

At least 19 recordsLinked to original sources
PubMed2001

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

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

Coronary Angiography↗
PubMed2001

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

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

Aged↗
PubMed2001

Determination of a weight-adjusted dose of TNK-tissue plasminogen activator.

BACKGROUND: TNK-tissue plasminogen activator (TNK-tPA) is a potent new thrombolytic agent for treatment of acute myocardial infarction. TNK-tPA was evaluated in 4214 patients in two dose-ranging trials (Thrombolysis in Myocardial Infarction [TIMI] 10B and Assessment of the Safety and Efficacy of a New Thrombolytic Agent [ASSENT] I). This article describes the rationale for the weight-adjusted dosing regimen of TNK-tPA that was selected for evaluation in the large phase III clinical trial ASSENT II. METHODS: Weight-based analyses were conducted with data from both the angiographic TIMI 10B trial, which compared TNK-tPA in doses of 30 mg, 40 mg, and 50 mg with the accelerated regimen of tPA in 889 patients, and the ASSENT I trial, which evaluated the safety of TNK-tPA in doses of 30 mg, 40 mg, and 50 mg in 3301 patients. Graphic and statistical analytic methods were used to assess relationships between weight and efficacy or safety measurements. RESULTS: The plasma clearance, initial plasma concentrations, and plasma steady-state volume of distribution all increased with decreasing body weight (all P<.001). The corrected TIMI frame count decreased (flow was faster) (P =.001) and the TIMI grade 3 flow increased with an increasing weight-standardized dose of TNK-tPA (P<.008). Mortality was inversely related to dose, but this relationship was not statistically significant. There was no clear relationship between intracranial hemorrhage and dose and weight. Serious bleeding events increased with increasing weight-standardized dose (P<.02). CONCLUSIONS: On the basis of these analyses, a weight-adjusted dosing regimen was devised for TNK-tPA that included five dosing increments and was based on a target weight-standardized dose of 0.53 mg/kg.

Aged↗
PubMed2001

Abciximab and early adjunctive percutaneous coronary intervention are associated with improved ST-segment resolution after thrombolysis: Observations from the TIMI 14 Trial.

BACKGROUND: Percutaneous coronary intervention (PCI) improves clinical outcomes in selected patients with failed thrombolysis but has not been proven to benefit patients who achieve a patent infarct-related artery. Even after successful epicardial reperfusion, myocardial perfusion may be inadequate. We sought to evaluate whether a strategy that uses a reperfusion regimen containing abciximab and a reduced-dose thrombolytic agent (combination therapy), followed by early adjunctive PCI, would result in improved myocardial perfusion, as assessed by ST-segment resolution. METHODS: ST resolution from 90 to 180 minutes after therapy was calculated for all 410 patients from the TIMI 14 trial who had evaluable electrocardiograms at both time points and who were treated with alteplase or reteplase. Patients were grouped according to whether they were treated with combination therapy or full-dose thrombolytic agent alone and whether they underwent PCI between the 90- and 180-minute electrocardiographic measurements. RESULTS: Among 105 patients who underwent adjunctive PCI between 90 and 180 minutes, mean ST resolution from 90 to 180 minutes was significantly greater in those who had received combination therapy versus those who had received full-dose thrombolytic alone (54% vs 8%; P =.002). Among 241 patients with TIMI grade 3 flow in the infarct-related artery at 90 minutes, adjunctive PCI significantly improved mean ST resolution in patients who had been treated with combination therapy (57% [PCI] vs 24% [no PCI]; P =.006), but PCI did not have this effect in patients who had received thrombolytic therapy alone (1% [PCI] vs 10% [no PCI]; P =.70). In a multivariate model controlling for factors that would be expected to independently influence 90- to 180-minute ST resolution, abciximab treatment remained significantly associated with greater ST resolution (P =.008). CONCLUSIONS: A strategy that uses a combination reperfusion regimen that includes abciximab, followed by early adjunctive PCI, is associated with greater ST-segment resolution, which may reflect enhanced tissue level and microvascular perfusion. Future studies should evaluate prospectively the clinical efficacy of this strategy.

Abciximab↗
PubMed2000

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

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

Angina, Unstable↗
PubMed2000

Impact of injections during diagnostic coronary arteriography on coronary patency in the setting of acute myocardial infarction from the TIMI trials. Thrombolysis In Myocardial Infarction.

The mechanical force of injection at 90 minutes opens 13.4% of occluded arteries, but overall, only 2.4% of all culprit arteries (already open and occluded combined) are opened. Thus, although some arteries are opened by the force of hand injection, the frequency of mechanical opening among all arteries is low, and hand injections appear to alter current 80% patency rates by approximately 2.5%.

Abciximab↗
PubMed2000

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.

BACKGROUND: Elevation of the white blood cell (WBC) count during acute myocardial infarction (AMI) is associated with adverse outcomes. We examined the relationship between the WBC count and angiographic findings to gain insight into this relationship. Results and Methods-We evaluated data from 975 patients in the Thrombolysis In Myocardial Infarction (TIMI) 10A and 10B trials. Patients with a closed artery at 60 and 90 minutes had higher a WBC count than patients with an open artery (P:=0.02). Likewise, the presence of angiographically apparent thrombus was associated with a higher WBC count (11.5+/-5.2x10(9)/L, n=290, versus 10.7+/-3. 5x10(9)/L, n=648; P=0.008). In addition, a higher WBC count was associated with poorer TIMI myocardial perfusion grades (4-way P=0.04). Mortality rates were higher in patients with a higher WBC count (0% for WBC count 0 to 5x10(9)/L, 4.9% for WBC count 5 to 10x10(9)/L, 3.8% for WBC count 10 to 15x10(9)/L, 10.4% for WBC count >15x10(9)/L; P=0.03). The development of new congestive heart failure or shock was also associated with a higher WBC count (0% for WBC count 0 to 5x10(9)/L, 5.2% for WBC count 5 to 10x10(9)/L, 6.1% for WBC count 10 to 15x10(9)/L, 17.1% for WBC count >15x10(9)/L; P<0.001), an observation that remained significant in a multivariable model that adjusted for potential confounding variables (odds ratio 1.21, P=0.002). CONCLUSIONS: Elevation in WBC count was associated with reduced epicardial blood flow and myocardial perfusion, thromboresistance (arteries open later and have a greater thrombus burden), and a higher incidence of new congestive heart failure and death. These observations provide a potential explanation for the higher mortality rate observed among AMI patients with elevated WBC counts and helps explain the growing body of literature that links inflammation and cardiovascular disease.

Coronary Angiography↗
PubMed2000

Degree of residual stenosis in the culprit coronary artery after thrombolytic administration (Thrombolysis In Myocardial Infarction [TIMI] trials).

This study was undertaken to characterize residual stenosis after thrombolytic administration and to evaluate clinical and angiographic features and early outcomes of patients with mild residual obstruction after thrombolytic administration. Patients who underwent angiography at 90 minutes after thrombolytic administration in the Thrombolysis In Myocardial Infarction 4, 10A, 10B, and 14 trials were divided into 3 groups according to the degree of residual stenosis measured by quantitative coronary angiography: patients with a patent culprit artery with <50% stenosis, patients with patent arteries and residual stenosis > or =50%, and patients with occluded arteries. Only 8.9% of the patients (188 of 2,119) had an infarct-related artery luminal diameter stenosis of <50% 90 minutes after thrombolysis. Compared with patients with patent arteries and > or =50% stenosis, patients with mild residual obstruction were younger (56.8 vs 58.6 years; p = 0.03), had fewer prior myocardial infarctions (6.9% vs 13.3%; p = 0.01), fewer eccentric (19.8% vs 42.1%; p <0.0001), ulcerated (7.5% vs 13.2%; p = 0.03), and collateralized (6.6% vs 13.2%, p = 0.01) lesions, but a greater thrombus burden (29.7% vs 18.3%, p = 0.0002). Among patients with patent arteries, a residual stenosis of <50% was associated with a significantly lower composite of in-hospital death, myocardial infarction, and congestive heart failure (2.8% vs 7.1%, p = 0.03). Thus, a minority of patients have a mild residual obstruction at 90 minutes after thrombolytic administration. These patients have less complex lesions with greater thrombus burdens and better clinical outcomes.

Clinical Trials as Topic↗
PubMed2000

Relationship of symptom-onset-to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acute myocardial infarction.

CONTEXT: Rapid time to treatment with thrombolytic therapy is associated with lower mortality in patients with acute myocardial infarction (MI). However, data on time to primary angioplasty and its relationship to mortality are inconclusive. OBJECTIVE: To test the hypothesis that more rapid time to reperfusion results in lower mortality in the strategy of primary angioplasty. DESIGN: Prospective observational study of data collected from the Second National Registry of Myocardial Infarction between June 1994 and March 1998. SETTING: A total of 661 community and tertiary care hospitals in the United States. SUBJECTS: A cohort of 27,080 consecutive patients with acute MI associated with ST-segment elevation or left bundle-branch block who were treated with primary angioplasty. MAIN OUTCOME MEASURE: In-hospital mortality, compared by time from acute MI symptom onset to first balloon inflation and by time from hospital arrival to first balloon inflation (door-to-balloon time). RESULTS: Using a multivariate logistic regression model, the adjusted odds of in-hospital mortality did not increase significantly with increasing delay from MI symptom onset to first balloon inflation. However, for door-to-balloon time (median time 1 hour 56 minutes), the adjusted odds of mortality were significantly increased by 41% to 62% for patients with door-to-balloon times longer than 2 hours (for 121-150 minutes: odds ratio [OR], 1.41; 95% confidence interval [CI], 1.08-1.84; P=.01; for 151-180 minutes: OR, 1.62; 95% CI, 1.23-2.14; P<.001; and for >180 minutes: OR, 1.61; 95% CI, 1.25-2.08; P<.001). CONCLUSIONS: The relationship in our study between increased mortality and delay in door-to-balloon time longer than 2 hours (present in nearly 50% of this cohort) suggests that physicians and health care systems should work to minimize door-to-balloon times and that door-to-balloon time should be considered when choosing a reperfusion strategy. Door-to-balloon time also appears to be a valid quality-of-care indicator. JAMA. 2000.

Aged↗
PubMed2000

High levels of platelet inhibition with abciximab despite heightened platelet activation and aggregation during thrombolysis for acute myocardial infarction: results from TIMI (thrombolysis in myocardial infarction) 14.

BACKGROUND: We evaluated platelet activation and aggregation in patients with acute myocardial infarction (AMI) treated with thrombolytic therapy alone or with reduced-dose thrombolysis and concomitant abciximab. METHODS AND RESULTS: The study was performed in 20 control subjects and 51 patients with AMI before and after reperfusion with either alteplase or reteplase or reduced doses of these agents with concomitant abciximab. Platelet activation was assayed by platelet surface expression of P-selectin. Turbidometric platelet aggregation in response to ADP was measured in patients before thrombolytic therapy and 90 minutes and 24 hours after the beginning of thrombolytic therapy. P-selectin expression was greater at baseline in patients than normal control subjects (30.4% versus 9. 8%, P<0.0001) but was identical between the 2 groups after stimulation with ADP (64.4% versus 69.3%, P=0.37). However, at 24 hours, basal P-selectin expression declined in patients (P=0.0025 versus baseline), whereas ADP-stimulated P-selectin expression was lower in patients than in control subjects (48% versus 69%, P=0. 0004). When combined with reduced doses of either alteplase or reteplase, abciximab achieved 91% and 83% inhibition of 5 and 20 micromol/L ADP-induced platelet aggregation, which decreased to 46% and 40%, respectively, at 24 hours. No appreciable difference in the platelet inhibition profile of abciximab was observed between the 2 thrombolytics. CONCLUSIONS: Platelet activation and aggregation are heightened in the setting of thrombolysis for AMI. Despite this enhanced level of platelet activation, abciximab, combined with a reduced-dose thrombolytic, inhibited platelet aggregation similarly to the level reported in elective settings.

Abciximab↗
PubMed2000

Microvascular dysfunction in acute myocardial infarction: focus on the roles of platelet and inflammatory mediators in the no-reflow phenomenon.

Recent interest has shifted from infarct artery patency to microvascular perfusion in the evaluation of patients with acute myocardial infarction (AMI). Microvascular dysfunction occurs in a substantial proportion of patients, despite aggressive therapy with thrombolytic agents and/or percutaneous mechanical revascularization techniques. Patients with impaired microvascular perfusion after immediate reperfusion therapy have an adverse clinical prognosis. Recent studies have extended our understanding of the pathophysiology of this so-called no-reflow phenomenon, focusing on the critical roles of platelet and inflammatory mediators leading to microvascular obstruction and reperfusion injury. Moving beyond the Thrombolysis in Myocardial Infarction (TIMI) flow grade system, new techniques have been developed to assess microvascular perfusion, including TIMI frame counting, angiographic myocardial perfusion grading, myocardial contrast echocardiography, Doppler flow wire studies, nuclear scintigraphy, and magnetic resonance imaging. Armed with a greater understanding of the primary mediators of microvascular dysfunction, these tools may identify improved therapy directed at optimizing myocardial perfusion in patients with AMI.

Capillary Permeability↗
PubMed2000

ST-segment resolution and infarct-related artery patency and flow after thrombolytic therapy. Thrombolysis in Myocardial Infarction (TIMI) 14 investigators.

Because patients who fail to achieve reperfusion after thrombolytic therapy remain at high risk for morbidity and mortality, noninvasive measures of infarct-related artery (IRA) patency are needed to identify candidates for rescue interventions. We prospectively studied 444 patients from the Thrombolysis In Myocardial Infarction (TIMI) 14 trial with interpretable baseline and 90 minute 12-lead electrocardiograms. The percent resolution of ST-segment deviation from baseline to 90 minutes was compared with 90-minute IRA TIMI flow grade, as determined in an angiographic core laboratory. Patients with complete (> or = 70%) ST resolution (n = 208; 47%) had a patency (TIMI 2 or 3 flow) rate of 94%, a TIMI 3 flow rate of 79%, and a 30-day mortality rate of 1.0%. Patients with partial (30% to 70%) or no (< or = 30%) ST resolution had significantly lower rates of patency (72% and 68%; p < 0.0001 vs complete ST resolution) and TIMI 3 flow (50% and 44%; p < 0.0001 vs complete ST resolution), and higher 30-day mortality (4.2% and 5.9%; p = 0.01 vs complete ST resolution). With use of electrocardiographic criteria alone, approximately 50% of patients can be classified as having a high (94%) probability of IRA patency and a very low risk for mortality. Angiography to determine patency of the IRA may be unnecessary in these patients. In patients without complete (> or = 70%) ST resolution, the IRA is still likely to be patent, and additional information from clinical variables or serum markers may help to identify candidates for coronary angiography. Patients with persistent ST elevation despite a patent IRA are at increased risk for mortality, likely due to extensive microvascular and tissue injury.

Abciximab↗
PubMed2000

Abciximab improves both epicardial flow and myocardial reperfusion in ST-elevation myocardial infarction. Observations from the TIMI 14 trial.

BACKGROUND: In the presence of ST-elevation myocardial infarction, patients with successful epicardial reperfusion (TIMI 3 flow) but persistent ST elevation on a 12-lead ECG are at high risk for subsequent death and left ventricular dysfunction. In the TIMI 14 trial, a dose-ranging angiographic study, combined therapy with abciximab plus reduced-dose tPA enhanced the speed and efficacy of epicardial reperfusion. We determined whether the combination of abciximab plus reduced-dose tPA provided additional benefit in terms of myocardial reperfusion, as evidenced by greater resolution of ST elevation. METHODS AND RESULTS: All 346 patients with interpretable baseline and 90-minute ECGs, treated with either tPA alone or abciximab plus reduced-dose tPA (combination therapy), were included. Patients receiving combination therapy (n=221) had a 59% rate of complete (>/=70%) ST resolution at 90 minutes versus 37% in those treated with tPA alone (n=125) (P<0.0001). When the analysis was limited to patients with TIMI 3 flow, patients treated with combination therapy (n=151) remained significantly more likely to achieve complete ST resolution than those receiving tPA alone (n=80) (69% versus 44%; P=0.0002). CONCLUSIONS: Combination therapy with abciximab and reduced-dose tPA improves myocardial (microvascular) reperfusion, as reflected in greater ST-segment resolution, in addition to epicardial flow. This finding may translate into improved clinical outcomes by enhancing myocardial salvage.

Abciximab↗
PubMed2000

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

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

Aged↗