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W D Weaver

Publications and source records attributed to W D Weaver.

At least 37 records · Page 2Linked to original sources

Left ventricular thrombus and subsequent thromboembolism in patients with severe systolic dysfunction.

STUDY OBJECTIVES: To determine the frequency of left ventricular (LV) thrombi by echocardiography and to define the predictors of LV thrombus and subsequent thromboembolism. DESIGN: Retrospective case-control design. SETTING: Single tertiary care center. PATIENTS: Twenty-eight patients with LV thrombus in a consecutive series of 144 patients with severe LV dysfunction and follow-up period for a mean of 27.6 months. MEASUREMENTS AND RESULTS: Thirty-five clinical and echocardiographic variables were evaluated. The mean age of patients with (n = 28) vs patients without (n = 116) LV thrombus was 50.3 +/- 11.0 years vs 54.2 +/- 11.1 years (p = 0.09), with 22 patients (78.6%) and 78 patients (67.2%) being male (p = 0.24), respectively. The mean ejection fraction (EF) for those with vs those without LV thrombus was 17.5 +/- 5.5 vs 20.0 +/- 6.9 (p = 0. 08), with 16 patients (57.1%) and 42 patients (36.2%) having an EF < 20% (p = 0.04), respectively. The groups were similar with respect to other baseline characteristics, comorbid illnesses, and drug therapies other than anticoagulants. All 28 patients with LV thrombus (100%) and 54 of those without LV thrombus (46.6%) were treated with warfarin. Ischemic etiology of the cardiomyopathy (odds ratio, 4.78; 95% confidence interval, 1.51 to 15.11; p = 0.008) and increased LV internal diastolic dimension (LVIDD; odds ratio, 1.10; 95% confidence interval, 1.03 to 1.18; p = 0.004) were found to be independent predictors of thrombus formation. Peripheral embolism occurred in 5 patients (17.9%) vs 13 patients (11.2%) of those with and without LV thrombi, respectively (p = 0.35). Ischemic etiology of the cardiomyopathy (odds ratio, 3.79; 95% confidence interval, 1. 13 to 12.64; p = 0.03) and EF (odds ratio, 0.91; 95% confidence interval, 0.82 to 1.00; p = 0.04) were found to be independent predictors of systemic embolization. The patients with an embolic event suffered a significantly higher mortality (7 of 18 patients; 38.9%) during the follow-up period when compared to those without an embolic event (13 of 126 patients; 10.3%; p < 0.0001). CONCLUSIONS: We conclude that ischemic cardiomyopathy and dilated LV chamber sizes (LVIDD > 60 mm) are independently associated with LV thrombi. A peripheral embolic event is related to poor long-term survival in this patient group.

Adult↗

Risk stratification with a point-of-care cardiac troponin T test in acute myocardial infarction. GUSTOIII Investigators. Global Use of Strategies To Open Occluded Coronary Arteries.

Troponin T has been used successfully to risk stratify patients with acute coronary syndromes, but the utility of this approach using a rapid bedside assay in patients undergoing thrombolysis for ST-segment elevation acute myocardial infarction has not been assessed in a large population. We assessed whether a point-of-care, qualitative troponin T test at enrollment could independently risk-stratify patients randomized to receive alteplase or reteplase in the GUSTO-III trial. Complete troponin T data were available for 12,666 patients (84%) enrolled at 550 hospitals. The primary end point was mortality at 30 days, and the predictive ability of an elevated baseline troponin T level was analyzed (after adjustment for baseline characteristics) with multiple logistic regression. Patients with an elevated troponin T result at enrollment (8.9%) had significantly higher mortality at 30 days (unadjusted 15.7% vs 6.2% for negative patients; p = 0.001), which persisted even after adjustment for age, heart rate, location of infarction, Killip class, and systolic blood pressure. In a multivariable regression model, a positive troponin T result added independently to the prediction of 30-day mortality (chi-square 46, p = 0.001). A positive result with qualitative troponin T testing on admission is an independent marker of higher 30-day mortality. Troponin T testing could be a valuable addition to the evaluation strategy for patients with acute myocardial infarction.

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Reperfusion therapy in patients with acute myocardial infarction and prior coronary artery bypass graft surgery (National Registry of Myocardial Infarction-2).

We reviewed data from the National Registry of Myocardial Infarction-2 to determine the differences in characteristics and outcomes in patients with acute myocardial infarction (AMI) who have undergone previous coronary artery bypass grafting (CABG), and those who have not, and between post-CABG patients who were treated with alteplase (recombinant tissue-type plasminogen activator [rt-PA]) and those who were treated with primary percutaneous transluminal coronary angioplasty (PTCA). Demographic, therapeutic, and outcome data from patients with AMI were collected at > 1,000 hospitals in the United States in collaboration with National Registry of Myocardial Infarction-2. Of the 45,925 patients receiving reperfusion therapy, 2,544 of the 39,574 treated with rt-PA (6.4%) had a history of CABG, and 375 of the 6,351 treated with primary PTCA (5.9%) had a history of CABG. Patients with a history of CABG were older, more likely to be men, and had more comorbidities, but prior CABG was still an independent predictor of mortality after multivariate regression analysis (odds ratio 1.23; 95% confidence interval 1.05 to 1.44). Among the post-CABG patients who received rT-PA or underwent PTCA, there was no significant difference in in-hospital mortality rate or the combined end point of death and nonfatal stroke. Thus, (1) prior CABG is an independent predictor of mortality, and (2) for post-CABG patients with AMI who are not in shock and who are lytic-eligible, reperfusion therapy with rt-PA and PTCA result in similar outcomes with regard to in-hospital mortality and the combined end point of death and nonfatal stroke.

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Weight-adjusted dosing of TNK-tissue plasminogen activator and its relation to angiographic outcomes in the thrombolysis in myocardial infarction 10B trial. TIMI 10B Investigators.

Fixed doses of thrombolytic agents are generally administered to patients of varying body weights, and the dose-response relation may be confounded by the variability in patient weight. We hypothesized that higher doses of TNK-tissue plasminogen activator (tPA) per unit body weight would be related to improved flow at 90 minutes after thrombolytic administration. A total of 886 patients with acute myocardial infarction were randomized to receive either a single bolus of 30, 40, or 50 mg of TNK-tPA or front-loaded tPA in the Thrombolysis In Myocardial Infarction (TIMI) 10B trial. The dose of TNK-tPA administered was divided by the patient's weight to arrive at the TNK-tPA dose (mg) per unit body weight (kg), and patients were stratified into tertiles based on mg/kg of TNK-tPA: low dose, 0.2 to 0.39 mg/kg; mid-dose, 0.40 to 0.51 mg/kg; high dose, 0.52 to 1.24 mg/kg. Flow in the culprit and nonculprit arteries was analyzed using the TIMI flow grades and the corrected TIMI frame count (CTFC). The median CTFC in culprit arteries differed between the tertiles (3-way p = 0.007), with the CTFC being 7.2 frames faster in high-dose than in low-dose patients (43.1 +/- 30.1, median 31.2, n = 171 vs 54.6 +/- 34.8, median 38.4, n = 166, 2-way p = 0.002). Patients in the mid- and high-dose tertiles achieved patency more frequently (TIMI grade 2 or 3 flow) by 60 minutes (p = 0.02), and the 90-minute percent diameter stenosis was less severe in patients in the high- versus low-dose tertile (p = 0.03). In nonculprit arteries, the CTFC was faster in high- than in low-dose tertiles (29.6 +/- 13.4, median 26.9, n = 130 vs 34.7 +/- 16.3, median 32.8, n = 108, 3-way p = 0.03, 2-way p = 0.008). In patients who underwent percutaneous transluminal coronary angioplasty (PTCA), the CTFC in culprit arteries after PTCA was fastest in the high- and mid-dose tertiles than in those receiving low doses (2-way p = 0.05). Thus, higher doses per unit body weight of TNK-tPA result in not only faster culprit artery flow, but also faster nonculprit, global, and post-PTCA flow, which may reflect earlier opening, reduced stunning, or improved microvascular function. The greater effectiveness of thrombolysis must be weighed against any increase in risk.

Adult↗

Sex, clinical presentation, and outcome in patients with acute coronary syndromes. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes IIb Investigators.

BACKGROUND: Studies have reported that women with acute myocardial infarction have in-hospital and long-term outcomes that are worse than those of men. METHODS: To assess sex-based differences in presentation and outcome, we examined data from the Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes IIb study, which enrolled 12,142 patients (3662 women and 8480 men) with acute coronary syndromes, including infarction with ST-segment elevation, infarction with no ST-segment elevation, and unstable angina. RESULTS: Overall, the women were older than the men, and had significantly higher rates of diabetes, hypertension, and prior congestive heart failure. They had significantly lower rates of prior myocardial infarction and were less likely ever to have smoked. A smaller percentage of women than men had infarction with ST elevation (27.2 percent vs. 37.0 percent, P<0.001), and of the patients who presented with no ST elevation (those with myocardial infarction or unstable angina), fewer women than men had myocardial infarction (36.6 percent vs. 47.6 percent, P<0.001). Women had more complications than men during hospitalization and a higher mortality rate at 30 days (6.0 percent vs. 4.0 percent, P<0.001) but had similar rates of reinfarction at 30 days after presentation. However, there was a significant interaction between sex and the type of coronary syndrome at presentation (P=0.001). After stratification according to coronary syndrome and adjustment for base-line variables, there was a nonsignificant trend toward an increased risk of death or reinfarction among women as compared with men only in the group with infarction and ST elevation (odds ratio, 1.27; 95 percent confidence interval, 0.98 to 1.63; P=0.07). Among patients with unstable angina, female sex was associated with an independent protective effect (odds ratio for infarction or death, 0.65; 95 percent confidence interval, 0.49 to 0.87; P=0.003). CONCLUSIONS: Women and men with acute coronary syndromes had different clinical profiles, presentation, and outcomes. These differences could not be entirely accounted for by differences in base-line characteristics and may reflect pathophysiologic and anatomical differences between men and women.

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Combined historical and electrocardiographic timing of acute anterior and inferior myocardial infarcts for prediction of reperfusion achievable size limitation.

The historical time of acute symptom onset is not always an accurate indication of the timing of onset of an acute myocardial infarction (AMI). Consideration of electrocardiographic (ECG) timing parameters could supplement historical timing alone as a clinical guide for decisions regarding the use of reperfusion therapy. Three hundred ninety-five patients from 4 trials of thrombolytic therapy conducted in the northwestern United States and western Canada are included in the present study. A total of 316 patients received either streptokinase or tissue plasminogen activator, and 79 received no reperfusion therapy. Historical time of symptom onset was acquired by emergency or cardiology department personnel and recorded on patient report forms. An ECG method for estimating the timing of the AMI, the Anderson-Wilkins (AW) acuteness score, was calculated from the initial standard 12-lead recording by investigators blinded to the knowledge of symptom duration or any other study variables. Tomographic thallium-201 imaging 7 weeks after hospital admission was used to measure final AMI size. The ECG timing method achieved a relation with final AMI size similar to that previously reported for historical timing. The AW acuteness score proved most useful for anterior AMI location when there was a > or = 2 hour delay following symptom onset, but was most useful for the inferior AMI location when there was a < 2 hour delay. Despite a longer delay, patients with high AW acuteness scores had 50% lower final anterior AMI size than those with low scores; and despite a shorter delay, those with low ECG acuteness scores had 50% greater final inferior AMI size than those with high scores. The AW acuteness score combined with the historical estimation of symptom duration should provide a more accurate basis for predicting the potential for limitation of final AMI size than either method alone. These results could potentially provide the basis for developing a new method for noninvasive guidance of clinical decisions regarding administration of reperfusion therapy in the initial evaluation of patients with AMI.

Electrocardiography↗

Effects of stroke on medical resource use and costs in acute myocardial infarction. GUSTO I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Study.

BACKGROUND: Stroke occurs concurrently with myocardial infarction (MI) in approximately 30 000 US patients each year. This number is expected to rise with the increasing use of thrombolytic therapy for MI. However, no data exist for the economic effect of stroke in the setting of acute MI (AMI). The purpose of this prospective study was to assess the effect of stroke on medical resource use and costs in AMI patients in the United States. METHODS AND RESULTS: Medical resource use and cost data were prospectively collected for 2566 randomly selected US GUSTO I patients (from 23 105 patients) and for the 321 US GUSTO I patients who developed non-bypass surgery-related stroke during the baseline hospitalization. Follow-up was for 1 year. All costs are expressed in 1993 US dollars. During the baseline hospitalization, stroke was associated with a reduction in cardiac procedure rates and an increase in length of stay, despite a hospital mortality rate of 37%. Together with stroke-related procedural costs of $2220 per patient, the baseline medical costs increased by 44% ($29 242 versus $20 301, P<0.0001). Follow-up medical costs were substantially higher for stroke survivors ($22 400 versus $5282, P<0.0001), dominated by the cost of institutional care. The main determinant for institutional care was discharge disability status. The cumulative 1-year medical costs for stroke patients were $15 092 higher than for no-stroke patients. Hemorrhagic stroke patients had a much higher hospital mortality rate than non-hemorrhagic stroke patients (53% versus 15%, P<0.001), which was associated with approximately $7200 lower mean baseline hospitalization cost. At discharge, hemorrhagic stroke patients were more likely to be disabled (68% versus 46%, P=0.002). CONCLUSIONS: In this first large prospective economic study of stroke in AMI patients, we found that strokes were associated with a 60% ($15 092) increase in cumulative 1-year medical costs. Baseline hospitalization costs were 44% higher because of longer mean lengths of stay. Stroke type was a key determinant of baseline cost. Follow-up costs were more than quadrupled for stroke survivors because of the need for institutional care. Disability level was the main determinant of institutional care and thus of follow-up costs.

Activities of Daily Living↗

Neurosurgical evacuation of intracranial hemorrhage after thrombolytic therapy for acute myocardial infarction: experience from the GUSTO-I trial. Global Utilization of Streptokinase and tissue-plasminogen activator (tPA) for Occluded Coronary Arteries.

BACKGROUND: Intracranial hemorrhage is an uncommon but very dangerous complication in patients receiving thrombolytic therapy for acute myocardial infarction. Neurosurgical evacuation is often an available treatment option. However, the association between neurosurgical evacuation and clinical outcomes in these patients has yet to be determined. METHODS: The GUSTO-I trial randomly assigned 41,021 patients with acute myocardial infarction to 1 of 4 thrombolytic strategies in 1081 hospitals in 15 countries. A total of 268 patients (0.65%) had an intracranial hemorrhage. We assessed differences in clinical characteristics, neuroimaging features, Glasgow coma scale scores, functional status (disabled: moderate or severe deficit; not disabled: no or minor deficit) and 30-day mortality rate between the 46 patients who underwent neurosurgical evacuation and the 222 patients who did not. RESULTS: Mortality rate at 30 days for all patients with intracranial hemorrhage was 60%; an additional 27% were disabled. Evacuation was associated with significantly higher 30-day survival (65% versus 35%, P <.001) and a trend toward improved functional status (nondisabling stroke: 20% versus 12%, P =.15). CONCLUSIONS: Although intracranial hemorrhage is uncommon after thrombolysis for acute myocardial infarction, 87% of patients die or have disabling stroke. Although not definitive, these data indicate that neurosurgical evacuation may be associated with improved clinical outcomes. Physicians treating such patients should consider early neurosurgical consultation and intervention in these patients.

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Efegatran sulfate as an adjunct to streptokinase versus heparin as an adjunct to tissue plasminogen activator in patients with acute myocardial infarction. ESCALAT Investigators.

BACKGROUND: Previous clinical studies have shown that direct antithrombins can accelerate clot lysis after treatment with streptokinase in acute myocardial infarction (MI). Efegatran is a new direct antithrombin, which in experimental animals has been shown to enhance thrombolysis, reduce rate of reocclusion, and limit infarct size. This study was designed to compare the efficacy of efegatran plus streptokinase versus heparin plus accelerated tissue plasminogen activator (TPA) in coronary reperfusion in acute MI. METHODS AND RESULTS: In this randomized, dose-finding study (n = 245), we initially explored 4 doses of efegatran sulfate in combination with streptokinase (1.5 million U) given intravenously within 12 hours of symptom onset. The optimal dosage group of 0.5 mg/kg per hour was expanded and compared with heparin plus accelerated TPA. The primary end point was complete patency (Thrombolysis In Myocardial Infarction [TIMI] grade 3) at 90 minutes after thrombolytic therapy, assessed in a core angiographic laboratory. Infarct-related vessel patency (TIMI grade 2 or 3) and complete patency (TIMI grade 3) were 73% and 40% in the efegatran/streptokinase group versus 79% and 53% in the heparin/TPA group (P = not significant). In-hospital mortality rate was 5% for the efegatran/streptokinase group versus 0% for the heparin/TPA group (P = not significant). Major bleeding occurred in 23% of patients in the efegatran/streptokinase group versus 11% in the heparin/TPA group (P = not significant). No intracranial hemorrhage occurred. CONCLUSIONS: The combination of efegatran plus streptokinase is not superior to the current therapy of heparin and accelerated TPA in achieving early patency. In addition, there is no indication that this experimental treatment can achieve better clinical outcome.

Antithrombins↗

Prediction of 30-day mortality among patients with thrombolysis-related intracranial hemorrhage.

BACKGROUND: Limited information exists on risk factors for mortality after thrombolysis-related intracranial hemorrhage. We wished to determine the characteristics associated with 30-day mortality after thrombolysis-related intracranial hemorrhage. METHODS AND RESULTS: We performed an observational analysis within a randomized trial of 4 thrombolytic therapies, conducted in 1081 hospitals in 15 countries. Patients presented with ST-segment elevation within 6 hours of symptom onset. Our population was composed of the 268 patients who had primary intracranial hemorrhage after thrombolysis. With univariable and multivariable analyses, we identified clinical and brain imaging characteristics that would predict 30-day mortality among these patients. CT or MRI were available for 240 patients (90%). The 30-day mortality rate was 59.7%. Glasgow Coma Scale score, age, time from thrombolysis to symptoms of intracranial hemorrhage, hydrocephalus, herniation, mass effect, intraventricular extension, and volume and location of intracranial hemorrhage were significant univariable predictors. Multivariable analysis of 170 patients with complete data, 98 of whom died, identified the following independent, significant predictors: Glasgow Coma Scale score (chi2, 19.3; P<0. 001), time from thrombolysis to intracranial hemorrhage (chi2, 15.8; P<0.001), volume of intracranial hemorrhage (chi2, 11.6; P<0.001), and baseline clinical predictors of mortality in the overall GUSTO-I trial (chi2, 10.3; P=0.001). The final model had a C-index of 0.931. CONCLUSIONS: This model provides excellent discrimination between patients who are likely to live and those who are likely to die after thrombolytic-related intracranial hemorrhage; this may aid in making decisions about the appropriate level of care for such patients.

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Estimating the proportion of post-myocardial infarction patients who may benefit from prophylactic implantable defibrillator placement from analysis of the CAST registry. Cardiac Arrhythmia Suppression Trial.

We defined the proportion of post-myocardial infarction patients who would have been eligible for the Multicenter Automatic Defibrillator Implantation Trial (MADIT) from a population of 94,797 patients with myocardial infarction entered into the Cardiac Arrhythmia Suppression Trial Registry. From this large population, only between 0.3% to 1.7% would have met strict eligibility criteria for MADIT.

Adult↗

Higher T-wave amplitude associated with better prognosis in patients receiving thrombolytic therapy for acute myocardial infarction (a GUSTO-I substudy). Global Utilization of Streptokinase and Tissue plasminogen Activator for Occluded Coronary Arteries.

Increased T-wave amplitude is one of the earliest electrocardiographic (ECG) changes following coronary artery occlusion. Therefore, higher T waves in the presenting electrocardiogram should represent earlier time to treatment and thus be associated with lower mortality following thrombolytic therapy. However, T-wave amplitude has never been evaluated as a prognostic marker in this setting. We examined clinical outcomes in 3,317 patients with acute myocardial infarction (AMI) who underwent thrombolysis in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) Study. Patients were classified as either those with high T waves or those with low T waves. Higher T waves were defined as those >98th percentile of the upper limit of normal. T-wave amplitude was also evaluated as a continuous variable according to infarct location (maximum T-wave amplitude) and as the amount of excess T-wave amplitude above normal (excess T-wave amplitude). Patients with higher T waves had lower 30-day mortality than those without (5.2% vs 8.6%, p = 0.001) and were less likely to develop congestive heart failure (15% vs 24%, p <0.001) or cardiogenic shock (6.1% vs 8.6%, p = 0.023). Higher maximum T-wave amplitude and excess T-wave amplitude were predictive of lower 30-day mortality (chi-square = 67, p <0.001 and chi-square = 33, p <0.001, respectively). These differences remain significant after controlling for other prognostic baseline ECG variables. In addition, T-wave amplitude added prognostic significance after controlling for time to treatment. T-wave amplitude, an often-overlooked component of the electrocardiogram, can add significant prognostic information in initial evaluation of patients with AMI.

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Use of reperfusion therapy for acute myocardial infarction in the United States: data from the National Registry of Myocardial Infarction 2.

BACKGROUND: There is clear evidence that reperfusion therapy improves survival in selected patients with an acute myocardial infarction. However, several studies have suggested that many patients with an acute myocardial infarction do not receive this therapy. Whether this underutilization occurs in patients appropriate for such therapy remains unclear. METHODS AND RESULTS: We examined the use of reperfusion therapy in patients with an acute myocardial infarction hospitalized at 1470 hospitals participating in the National Registry of Myocardial Infarction 2. We identified 84 663 patients who were eligible for reperfusion therapy as defined by diagnostic changes on the initial 12-lead ECG, presentation to the hospital within 6 hours from symptom onset, and no contraindications to thrombolytic therapy. Twenty-four percent of these eligible patients did not receive any form of reperfusion therapy (7.5% of all patients). When multivariate analyses were used, left bundle-branch block (odds ratio [OR]=0.22; 95% CI=0.20 to 0.24), lack of chest pain at presentation (OR=0.22; 95% CI=0.21 to 0.24), age >75 years (OR=0.40, 95% CI=0.36 to 0.43), female sex (OR=0.88, 95% CI=0.83 to 0.92), and various preexisting cardiovascular conditions were independent predictors that the patient would not receive reperfusion therapy. CONCLUSIONS: Reperfusion therapy may be underutilized in the United States. Increased use of reperfusion therapy could potentially reduce the unnecessarily high mortality rates observed in women, the elderly, and other patient groups with the highest risk of death from an acute myocardial infarction.

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