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Biomedical subjects

E M Ohman

Publications and source records attributed to E M Ohman.

At least 55 records · Page 3Linked to original sources

Predictors of cardiogenic shock after thrombolytic therapy for acute myocardial infarction.

OBJECTIVES: This study characterized clinical factors predictive of cardiogenic shock developing after thrombolytic therapy for acute myocardial infarction (AMI). BACKGROUND: Cardiogenic shock remains a common and ominous complication of AMI. By identifying patients at risk of developing shock, preventive measures may be implemented to avert its development. METHODS: We analyzed baseline variables associated with the development of shock after thrombolytic therapy in the Global Utilization of Streptikonase and Tissue-Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial. Using a Cox proportional hazards model, we devised a scoring system predicting the risk of shock. This model was then validated in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-III) cohort. RESULTS: Shock developed in 1,889 patients a median of 11.6 h after enrollment. The major factors associated with increased adjusted risk of shock were age (chi2 = 285, hazard ratio [95% confidence interval] 1.47 [1.40, 1.53]), systolic blood pressure (chi2 = 280), heart rate (chi2 = 225) and Killip class (chi2 = 161, hazard ratio 1.70 [1.52, 1.90] and 2.95 [2.39, 3.63] for Killip II versus I and Killip III versus I, respectively) upon presentation. Together, these four variables accounted for >85% of the predictive information. These findings were transformed into an algorithm with a validated concordance index of 0.758. Applied to the GUSTO-III cohort, the four variables accounted for > 95% of the predictive information, and the validated concordance index was 0.796. CONCLUSIONS: A scoring system accurately predicts the risk of shock after thrombolytic therapy for AMI based primarily on the patient's age and physical examination on presentation.

Aged↗

Inhibition of platelet aggregation with a glycoprotein IIb-IIIa antagonist does not prevent thrombin generation in patients undergoing thrombolysis for acute myocardial infarction.

Thrombin activity has been implicated as a mechanism for failed reperfusion and reocclusion following thrombolysis. Aggregating platelets provide a phospholipid surface on which prothrombin is cleaved to form thrombin. We examined markers of thrombin generation and activity in patients enrolled in a randomized, placebo-controlled, dose escalating trial of the platelet glycoprotein IIb-IIIa inhibitor eptifibatide (Integrilintrade mark) administered concomitantly with tissue plasminogen activator for the treatment of myocardial infarction. Measurements were obtained at baseline, at 90 minutes, and at 6, 12, and 24 hours after starting therapy. Eptifibatide inhibited platelet aggregation in response to 20 microM ADP. Levels of fibrinopeptide A (FPA), thrombin-antithrombin complexes (TAT), and prothrombin fragment 1.2 (F1.2) were not lower in patients treated with eptifibatide than in the control group. In the course of dose escalation, two groups of patients received the same 135 microg/kg bolus of eptifibatide, one with and one without a heparin bolus. FPA levels were dramatically lower in the heparin-treated patients. Levels of FPA, TAT, and F1.2 were not higher in patients with than in those without recurrent ischemia, or in patients without than in those with Thrombolysis in Myocardial Infarction (TIMI) grade 3 angiographic flow at 90 minutes. These data suggest that thrombin generation and activity persist following thrombolysis, despite inhibition of platelet aggregation, and that treatment with inhibitors of thrombin activity may be required even when glycoprotein IIb-IIIa inhibitors are used.

Cohort Studies↗

Lack of progress in cardiogenic shock: lessons from the GUSTO trials.

AIMS: We used the GUSTO-I and GUSTO-III databases to evaluate our performance in treating cardiogenic shock patients over much of the 1990s. METHODS AND RESULTS: GUSTO-I (1990-1993) and GUSTO-III (1995-1997) prospectively identified all patients with cardiogenic shock complicating acute myocardial infarction. Demographics, clinical presentation and outcomes for cardiogenic shock patients in the two trials were compared. Only patients enrolled with cardiogenic shock in countries common to both trials were included in these analysis. The 695 patients with cardiogenic shock in GUSTO-III were compared with the 2814 patients with cardiogenic shock in GUSTO-I. GUSTO-III patients were older (P=0.0001) and more likely to be diabetic (P=0.009) and hypertensive (P=0.025). They had a higher Killip class (P=0.002) and significantly greater index anterior infarction than cardiogenic shock patients enrolled in GUSTO-I. Time to treatment, presentation heart rate, and diastolic blood pressure were similar; however, systolic blood pressure at presentation was higher among GUSTO-III patients (P=0.002). Rates of coronary angiography, pulmonary artery catheterization, and mechanical ventilation declined in GUSTO-III compared with GUSTO-I (P=0.001); rates of angioplasty and bypass surgery were similar. Cardiogenic shock mortality in GUSTO-III was significantly higher than in GUSTO-I (62 vs 54%, P=0.001), as were rates of reinfarction (14 vs 11%, P=0.013) and recurrent ischaemia (35 vs 27%, P=0.00001). Mortality at non-U.S. sites (68 and 64%) was higher than at U.S. sites (53 and 50%) in both GUSTO-I and GUSTO-III studies, respectively. Angioplasty, bypass surgery, and balloon pump rates were lower for non-U.S. patients. CONCLUSIONS: Cardiogenic shock continues to be associated with high mortality in thrombolytic-treated patients. Lower mortality observed in the U.S.A. supports consideration for percutaneous and surgical revascularization.

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New atrial fibrillation after acute myocardial infarction independently predicts death: the GUSTO-III experience.

BACKGROUND: Atrial fibrillation (AF) or flutter occurring after myocardial infarction may occur alone or in association with other complications. Whether the arrhythmia portends a poor prognosis independent of other complications with contemporary therapy is unknown. METHODS AND RESULTS: As part of the Global Use of Strategies To Open occluded coronary arteries (GUSTO-III) trial, we evaluated whether postinfarction complications were associated with the subsequent development of AF and whether AF independently predicted death over periods of 30 days and 1 year. Information including exact timing was collected on deaths and major in-hospital postinfarction complications up to 30 days. Of the 13,858 patients with sinus rhythm at enrollment, 906 later had AF or flutter and 12, 952 did not. We compared outcomes between these 2 groups, adjusting for differences in baseline characteristics and prefibrillation complications. Worsening heart failure, hypotension, third-degree heart block, and ventricular fibrillation were independent predictors of new-onset AF. The unadjusted odds ratio (OR) for death among patients with versus those without AF was 2.74 (95% confidence interval [95% CI], 2.56-3.34). After adjusting for baseline differences, the OR was reduced to 1.63 (95% CI, 1.31-2.02). Adjustment for other in-hospital complications before the onset of AF further reduced the OR to 1.49 (95% CI, 1.17-1.89). CONCLUSIONS: Atrial fibrillation or flutter occurs secondary to other postinfarction complications but independently portends a worse prognosis. Prevention and management may improve outcome.

Aged↗

Combining necrosis and platelet markers for perfecting myocardial infarction rule out: how close are we?

Each year, at least 5 million patients in the United States present to hospital emergency departments with the complaint of chest pain, and more than 10% of them will be diagnosed with acute myocardial infarction. One of the foremost tasks of the emergency department physician is to avoid unnecessary admissions and concomitantly to minimize the number of patients discharged home inappropriately. Currently available diagnostic tools, including the electrocardiogram and myocardial markers, have several shortcomings, including low specificity, and delayed sensitivity for the timely detection of myocardial necrosis. Therefore, the search for better methods of rapidly identifying patients with unstable coronary syndromes is one of the utmost priorities of modern emergency medicine. Available biochemical diagnostic tools are discussed in this review, focusing on the potential benefits of combining myocardial necrosis markers with indicators of platelet activation. It is hypothesized that such a combined approach may be more powerful in myocardial infarction risk stratification than separate marker determination.

Biomarkers↗

Temporal evolution in the management of acute ST elevation myocardial infarction: the seven-year GUSTO experience from canada and the united states. The North American GUSTO-I and GUSTO-III investigators.

BACKGROUND: Temporal changes in baseline characteristics, treatment and clinical outcomes of patients presenting with acute ST elevation myocardial infarction in Canada and the United States have not been examined comprehensively over time. OBJECTIVES: To evaluate baseline characteristics, process of care and clinical outcomes. Also, to explore whether earlier process-of-care differences between Canada and the United States had changed and, if so, whether they influenced clinical outcomes. PATIENTS AND METHODS: A total of 13, 888 American and 3011 Canadian patients enrolled in 184 American and 38 Canadian hospitals that participated in both the Global Utilization of Streptokinase and Tissue Plasminogen Activator (alteplase) for Occluded Coronary Arteries (GUSTO-I) trial (1990 to 1993) and the Global Utilization of Strategies to Open Occluded Coronary Arteries (GUSTO-III) trial (1995 to 1997) were studied. Logistic regression was used to identify significant prognostic factors, to assess illness severity at hospital presentation and to classify trends between Canada and the United States. RESULTS: In both countries, illness severity on admission increased, door-to-needle time for thrombolysis was reduced, intensive care unit stay was shortened and hospital stay decreased from GUSTO-I to GUSTO-III. Whereas the administration of oral nitrates, calcium blockers and beta-blockers at discharge converged over time between countries, the disparity in the use of angiography and revascularization widened; the rise in American revascularization rate was most evident in patients without in-hospital ischemia. The 30-day and one-year mortality rates were comparable and declined nonsignificantly in both countries. CONCLUSIONS: Despite increased illness severity and varying medication and procedure rates, there was no increase over time in 30-day or one-year mortality; this remained comparable between countries throughout the seven-year observation period.

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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.

Aged↗

Outcome of Hispanic patients treated with thrombolytic therapy for acute myocardial infarction: results from the GUSTO-I and III trials. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries.

OBJECTIVES: We sought to describe the differences in the process of care and clinical outcomes between Hispanics and non-Hispanics receiving thrombolytic therapy for myocardial infarction (MI). BACKGROUND: Hispanics are the fastest growing and second largest minority in the U.S. but most cardiovascular disease data on Hispanics has been derived from retrospective studies and vital statistics. Despite their higher cardiovascular risk-factor profile, better outcomes after MI have been reported in Hispanics. METHODS: We studied the baseline characteristics, resource use and outcomes of 734 Hispanics and 27,054 non-Hispanics treated for MI in the GUSTO-I and -III trials. The primary end point of both trials was 30-day mortality. RESULTS: Hispanics were younger, shorter, lighter and more often diabetic and began thrombolysis 9 min later, compared with non-Hispanics. Measures of socioeconomic status (educational level, employment and health insurance) were lower among Hispanics. Fewer Hispanics than non-Hispanics underwent in-hospital angiography (70% vs. 74%, p = 0.013) or bypass surgery (11% vs. 13.5%, p = 0.04). Hispanics received more angiotensin-converting enzyme (ACE) inhibitors and less calcium-channel blockers, prophylactic lidocaine and inotropic agents. Mortality at 30 days and at one year did not differ significantly between Hispanics and non-Hispanics (6.4% vs. 6.7% and 9.0% vs. 9.7%, respectively). We noted no interactions between thrombolytic strategy and Hispanic status on major outcomes (30-day death, stroke and major bleeding). CONCLUSIONS: The care of Hispanics with MI differed slightly from that of non-Hispanics. Nevertheless, these differences in care did not affect long-term outcomes.

Aged↗

Effectiveness of early coronary angioplasty and abciximab for failed thrombolysis (reteplase or alteplase) during acute myocardial infarction (results from the GUSTO-III trial). Global Use of Strategies To Open occluded coronary arteries.

We evaluated the effects of abciximab treatment during early angioplasty after clinically failed thrombolysis for acute myocardial infarction. In the Global Use of Strategies To Open occluded coronary arteries (GUSTO-III) trial of reteplase versus alteplase for acute infarction (n = 15,059), 392 patients underwent angioplasty a median of 3.5 hours after thrombolysis and had complete procedural data. We compared 30-day mortality and in-hospital outcomes between patients who received abciximab (n = 83) and those who did not (n = 309), and (among patients given abciximab) between those randomized to alteplase versus reteplase. Patients given abciximab had anterior infarction less often, but were more often in Killip classes III or IV. The 30-day mortality rate tended to be lower with abciximab (3.6% vs 9.7%, p = 0.076), more so after adjustment for baseline differences (p = 0.042). The composite of death, stroke, or reinfarction did not differ significantly with abciximab treatment (12% vs 14%, p = 0.7), but it occurred less often among abciximab-treated patients who had been randomized to reteplase (n = 55) versus alteplase (n = 28) (7% vs 21%, p = 0.08). Severe bleeding was increased among abciximab-treated patients (3.6% vs 1.0%, p = 0.08), despite less heparin use. No intracranial hemorrhages occurred with abciximab. The use of abciximab for early angioplasty after clinically failed thrombolysis resulted in trends toward lower 30-day mortality and increased bleeding.

Abciximab↗

Cardiac markers: point of care testing.

Point-of-care (POC) or "near-patient" testing allows diagnostic assays to be performed in locations such as the emergency department or intensive care unit where treatment decisions are made and care is delivered based on the results of these assays. Presently, there exist POC immunoassays for several cardiac markers including creatine kinase MB (CK-MB), myoglobin, troponin I, and troponin T that yield qualitative and quantitative results comparable to traditional central lab assays. In the evaluation of emergency room patients with chest pain, POC cardiac markers may improve triage and clinical outcomes. Existing POC assays combining myoglobin and CK-MB have high sensitivity and specificity for diagnosing acute myocardial infarction and may provide the earliest identification of myocardial injury. POC Troponin T assays are the most studied POC cardiac marker assays. Along with POC troponin I assays, these tests provide more sensitive identification of myocardial injury and valuable prognostic information. Prior studies of POC cardiac marker assays have not addressed whether POC testing affects patient outcome or process of care. In situations in which caregivers base triage, treatment and monitoring decisions on time-sensitive diagnostic results, POC tests linked with improved triage and treatment strategies may improve resource utilization and clinical outcomes.

Biomarkers↗

Prognostic value of the admission electrocardiogram in acute coronary syndromes.

CONTEXT: The presence of ischemic changes on electrocardiogram (ECG) correlates with poorer outcomes in patients with acute chest pain. OBJECTIVE: To determine the prognostic value of various ECG presentations of acute myocardial ischemia. DESIGN: Retrospective analysis of the presenting ECGs of patients enrolled in Global Use of Strategies To Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb). SETTING: Three hundred seventy-three hospitals in 13 countries in North America, Europe, Australia, and New Zealand. PATIENTS: A total of 12142 patients who reported symptoms of cardiac ischemia at rest within 12 hours of admission and had signs of myocardial ischemia confirmed by ECG. On presenting ECG, 22% of patients had T-wave inversion, 28% had ST-segment elevation, 35% had ST-segment depression, and 15% had a combination of ST-segment elevation and depression. MAIN OUTCOME MEASURE: Ability of presenting ECG to predict death or myocardial reinfarction during the first 30 days of follow-up. RESULTS: The 30-day incidence of death or myocardial reinfarction was 5.5% in patients with T-wave inversion, 9.4% in those with ST-segment elevation, 10.5% in those with ST-segment depression, and 12.4% in those with ST-segment elevation and depression (P<.001). After adjusting for factors associated with an increased risk of 30-day death or reinfarction, compared with those who had T-wave inversion only, the odds of 30-day death or reinfarction were 1.68 (95% confidence interval [CI], 1.36-2.08) in those with ST-segment elevation, 1.62 (95% CI, 1.32-1.98) for those with ST-segment depression, and 2.27 (95% CI, 1.80-2.86) for those with combined elevation and depression. An elevated creatine kinase level at admission correlated with a higher risk of death (odds ratio [OR], 2.36; 95% CI, 1.92-2.91) and death or reinfarction (OR, 1.56; 95% CI, 1.32-1.85). The ECG category and creatine kinase level at admission remained highly predictive of death and myocardial infarction after multivariate adjustment for the significant baseline predictors of events. CONCLUSIONS: The ECG at presentation allows immediate risk stratification across the spectrum of acute coronary syndromes. An elevated creatine kinase level at admission is associated with worse outcomes.

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Hemodynamic effects of new intra-aortic balloon counterpulsation timing methods in patients: a multicenter evaluation.

BACKGROUND: To test whether later intra-aortic balloon pump (IABP) deflation approaching or simultaneous with left ventricular ejection would improve hemodynamics and myocardial efficiency with the use of new balloon deflation methods, 4 IABP timing techniques were evaluated in 43 patients. METHODS AND RESULTS: Later balloon deflation produced significantly greater percentage changes in mean aortic pressure (6% vs 1%), systolic pressure time index (-27% vs -20%), diastolic pressure time index (35% vs 19%), and the systolic pressure-time index/diastolic pressure-time index ratio (97% vs 51%), respectively. However, these changes increased peak systolic pressure (-15% vs -11%). Cardiac output and stroke volume indexes were not significantly altered over the 4 settings. CONCLUSIONS: These data suggest that systemic hemodynamics and myocardial efficiency may be improved by later balloon deflation approaching left ventricular ejection in comparison to conventional IABP timing.

Adult↗

Clinical outcomes after detection of elevated cardiac enzymes in patients undergoing percutaneous intervention. IMPACT-II Investigators. Integrilin (eptifibatide) to Minimize Platelet Aggregation and Coronary Thrombosis-II.

OBJECTIVES: We examined the relations of elevated creatine kinase (CK) and its myocardial band isoenzyme (CK-MB) to clinical outcomes after percutaneous coronary intervention (PCI) in patients enrolled in Integrilin (eptifibatide) to Minimize Platelet Aggregation and Coronary Thrombosis-II (trial) (IMPACT-II), a trial of the platelet glycoprotein IIb/IIIa inhibitor eptifibatide. BACKGROUND: Elevation of cardiac enzymes often occurs after PCI, but its clinical implications are uncertain. METHODS: Patients undergoing elective, scheduled PCI for any indication were analyzed. Parallel analyses investigated CK (n=3,535) and CK-MB (n=2,341) levels after PCI (within 4 to 20 h). Clinical outcomes at 30 days and 6 months were stratified by postprocedure CK and CK-MB (multiple of the site's upper normal limit). RESULTS: Overall, 1,779 patients (76%) had no CK-MB elevation; CK-MB levels were elevated to 1 to 3 times the upper normal limit in 323 patients (13.8%), to 3 to 5 times normal in 84 (3.6%), to 5 to 10 times normal in 86 (3.7%), and to >10 times normal in 69 patients (2.9%). Elevated CK-MB was associated with an increased risk of death, reinfarction, or emergency revascularization at 30 days, and of death, reinfarction, or surgical revascularization at 6 months. Elevated total CK to above three times normal was less frequent, but its prognostic significance paralleled that seen for CK-MB. The degree of risk correlated with the rise in CK or CK-MB, even for patients with successful procedures not complicated by abrupt closure. CONCLUSIONS: Elevations in cardiac enzymes, including small increases (between one and three times normal) often not considered an infarction, are associated with an increased risk for short-term adverse clinical outcomes after successful or unsuccessful PCI.

Aged↗

Use of glycoprotein IIb/IIIa inhibition plus fibrinolysis in acute myocardial infarction.

Pharmacological reperfusion therapy for acute myocardial infarction with intravenous fibrinolytic agents improves survival yet fails to achieve early and complete coronary blood flow in nearly half of treated patients. In principle, glycoprotein (GP) IIb/IIIa inhibitors, potent antiplatelet agents, might improve the efficacy and clinical outcomes associated with fibrinolysis. Preclinical research suggests more rapid and effective reperfusion with combined platelet GP IIb/IIIa inhibition and fibrinolysis. Early clinical studies confirm improved early patency and more rapid electrocardiographic resolution, but increased bleeding complications, with the addition of GP IIb/IIIa antagonists to conventional fibrinolysis. Future studies may combine reduced-dose fibrinolytic therapy with GP IIb/IIIa inhibition to optimize efficacy and safety.

Abciximab↗