Faculty Bibliography

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

BACKGROUND: Cardiogenic shock is usually considered a sequela of ST-segment elevation myocardial infarction. There are limited prospective data on the incidence and significance of shock in non-ST-segment elevation patients. This study assessed the incidence and outcomes of cardiogenic shock developing after enrollment among patients with and without ST-segment elevation in the Global Use of Strategies To Open Occluded Coronary Arteries (GUSTO)-IIb trial. METHODS AND RESULTS: Among 12,084 patients in GUSTO-IIb who did not present with cardiogenic shock, 4092 (34%) had and 7991 (66%) did not have ST-segment elevation on the enrollment ECG. Cardiogenic shock developed in 4.2% of ST-segment elevation patients compared with 2.5% of patients without ST-segment elevation (odds ratio, 0. 581; 95% CI, 0.472 to 0.715; P<0.001). Shock developed significantly later among patients without ST-segment elevation. There were significant differences in baseline characteristics between shock patients with and without ST-segment elevation: Patients without ST-segment elevation were older, more frequently had diabetes mellitus and 3-vessel disease, but had less TIMI grade 0 flow at angiography. Regardless of the initial ECG, mortality was high: 63% among patients with ST-segment elevation and 73% in those without ST-segment elevation. CONCLUSIONS: Cardiogenic shock occurs in the setting of acute ischemic syndromes regardless of whether ST-segment elevation is present. The incidence, patient characteristics, timing, clinical course, and angiographic findings differ between the 2 groups. Mortality from cardiogenic shock is similarly high among patients with and without ST-segment elevation

The angiograms of 89 patients were reviewed from the LATE Ancillary Study (randomized trial of recombinant tissue plasminogen activator vs placebo in patients with symptom onset after 6 hours of myocardial infarction) to determine patency of the infarct-related artery (IRA). In the occluded IRA group (n = 35), the incidence of signal-averaged electrocardiographic abnormality (fQRS > 120 ms) was significantly higher (p = 0.04), the filtered QRS duration was significantly longer (p = 0.007), and the V40 was significantly shorter (p = 0.02), compared with the patent IRA group (n = 54)

BACKGROUND: The leading cause of death in patients hospitalized for acute myocardial infarction is cardiogenic shock. We conducted a randomized trial to evaluate early revascularization in patients with cardiogenic shock. METHODS: Patients with shock due to left ventricular failure complicating myocardial infarction were randomly assigned to emergency revascularization (152 patients) or initial medical stabilization (150 patients). Revascularization was accomplished by either coronary-artery bypass grafting or angioplasty. Intraaortic balloon counterpulsation was performed in 86 percent of the patients in both groups. The primary end point was mortality from all causes at 30 days. Six-month survival was a secondary end point. RESULTS: The mean age of the patients was 66+/-10 years, 32 percent were women and 55 percent were transferred from other hospitals. The median time to the onset of shock was 5.6 hours after infarction, and most infarcts were anterior in location. Ninety-seven percent of the patients assigned to revascularization underwent early coronary angiography, and 87 percent underwent revascularization; only 2.7 percent of the patients assigned to medical therapy crossed over to early revascularization without clinical indication. Overall mortality at 30 days did not differ significantly between the revascularization and medical-therapy groups (46.7 percent and 56.0 percent, respectively; difference, -9.3 percent; 95 percent confidence interval for the difference, -20.5 to 1.9 percent; P=0.11). Six-month mortality was lower in the revascularization group than in the medical-therapy group (50.3 percent vs. 63.1 percent, P=0.027). CONCLUSIONS: In patients with cardiogenic shock, emergency revascularization did not significantly reduce overall mortality at 30 days. However, after six months there was a significant survival benefit. Early revascularization should be strongly considered for patients with acute myocardial infarction complicated by cardiogenic shock

BACKGROUND: Recent trials have demonstrated an association between high activated partial thromboplastin time (aPTT) and bleeding, intracranial hemorrhage, reinfarction, and death in patients with acute coronary syndromes treated with heparin. Of all the factors that affect aPTT in patients treated with heparin, body weight is most strongly correlated. METHODS: We compared the efficacy of 2 weight-adjusted heparin regimens (groups 2 and 3) and the standard (group 1) non-weight-adjusted 5000-U intravenous bolus/1000 U/hr infusion to achieve an aPTT between 45 and 70 seconds in a nonrandomized prospective cohort of 80 patients admitted with unstable angina and non-ST elevation myocardial infarction. RESULTS: Patients treated with the lower dose of weight-adjusted heparin (60 U/kg intravenous bolus, maximum of 4000 U; 12 U/kg/hr, maximum 900 U/kg), group 3, were more often within the target range for aPTT at 6 hours (34% vs 5% vs 0%) and required fewer heparin infusion changes (1.0 +/- 1.0 vs 1.9 +/- 1.0 vs 2.0 +/- 0.9) within the first 24 hours compared with the other regimens. Patients in groups 1 and 2 were overwhelmingly above target range at 6 hours (95% and 84%, respectively, compared with 48% in group 3). CONCLUSIONS: Traditional heparin dosing regimens result in marked initial overanticoagulation in patients with acute coronary syndromes, which may place these patients at higher risk of adverse outcomes. A lower dose weight-adjusted heparin regimen is superior in achieving early aPTTs within the target range and reducing the need for infusion changes over the ensuing 24 hours

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

BACKGROUND: Current knowledge of predictors of death among patients with cardiogenic shock complicating myocardial infarction is limited. We aimed to develop a risk assessment prognostic algorithm of 30-day mortality, including clinical and hemodynamic data prospectively collected among patients with cardiogenic shock in the 41,021-patient Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial. METHODS: We used logistic regression modeling techniques to evaluate the relations between demographic, clinical, and hemodynamic characteristics and 30-day mortality rate for the entire shock population (n = 2968) and for patients who underwent right-heart catheterization (n = 995). RESULTS: The odds (95% confidence interval) of dying were 1.49 times higher (1.27-1.74) for patients 10 years older and 1.70 times higher (1.19-2.44) for patients with prior infarction. Findings derived from physical examination, such as altered sensorium and cold, clammy skin, were important independent predictors of prognosis (odds of dying 1.68 times higher for each [1.19-2.39 and 1.15-2.46]). The odds of dying were also 2.25 times higher (1.61-3.15) in patients with oliguria. Mortality rate was lowest for cardiac output and pulmonary capillary wedge measurements of 5.1 L/min and 20 mm Hg, respectively, and increased with either higher or lower values. Patients with shock had better outcomes than patients in whom shock developed later, although for the latter subgroup, prognosis was worse in patients who had heart failure (Killip class II to III). CONCLUSIONS: We devised a prognostic algorithm for patients with cardiogenic shock complicating acute myocardial infarction. In addition to demographic and easily derived physical examination features, data derived from right-heart catheterization added valuable information that increased the ability to predict outcome in this high-risk population

Aspirin is beneficial in the prevention and treatment of cardiovascular events, but patients who have events while taking aspirin may have worse outcomes than those not on aspirin. We investigated the association between prior aspirin use and clinical outcomes in 9,461 patients with non-ST-elevation acute coronary syndromes enrolled in the Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, before and after adjustment for baseline factors. We also examined whether eptifibatide has a differential treatment effect in prior aspirin users. Prior aspirin users were less likely to have an enrollment myocardial infarction (MI) (vs unstable angina) (43.9% vs 48.8%, p = 0.001) but more likely to have death or MI at 30 days (16.1% vs 13.0%, p = 0.001) and at 6 months (19.9% vs 15.9%, p = 0.001). After adjustment, prior aspirin users remained less likely to have an enrollment MI (odds ratio 0.88, 95% confidence interval 0.79 to 0.97) and more likely to have death or MI at 30 days (odds ratio 1.16, 95% confidence interval 1.00 to 1.33) but not at 6 months (odds ratio 1.14, 95% confidence interval 0.98 to 1.33). In a multivariable model, eptifibatide did not have a different treatment effect in prior aspirin users compared with nonusers (p = 0.534). Prior aspirin users had fewer enrollment MIs but worse long-term outcomes than nonusers. We found no evidence for a different treatment effect of eptifibatide in prior aspirin users

OBJECTIVES: The purpose of this study was to determine the incidence and demographic characteristics of patients experiencing cardiac rupture after thrombolytic and adjunctive anticoagulant therapy and to identify possible associations between the mechanism of thrombin inhibition (indirect, direct) and the intensity of systemic anticoagulation with its occurrence. BACKGROUND Cardiac rupture is responsible for nearly 15% of all in-hospital deaths among patients with myocardial infarction (MI) given thrombolytic agents. Little is known about specific patient- and treatment-related risk factors. METHODS Patients (n = 3,759) with MI participating in the Thrombolysis and Thrombin Inhibition in Myocardial Infarction 9A and B trials received intravenous thrombolytic therapy, aspirin and either heparin (5,000 U bolus, 1,000 to 1,300 U/h infusion) or hirudin (0.1 to 0.6 mg/kg bolus, 0.1 to 0.2 mg/kg/h infusion) for at least 96 h. A diagnosis of cardiac rupture was made clinically in patients with sudden electromechanical dissociation in the absence of preceding congestive heart failure, slowly progressive hemodynamic compromise or malignant ventricular arrhythmias. RESULTS A total of 65 rupture events (1.7%) were reported-all were fatal, and a majority occurred within 48 h of treatment Patients with cardiac rupture were older, of lower body weight and stature and more likely to be female than those without rupture (all p < 0.001). By multivariable analysis, age >70 years (odds ratio [OR] 3.77; 95% confidence interval [CI] 2.06, 6.91), female gender (OR 2.87; 95% CI 1.44, 5.73) and prior angina (OR 1.82; 95% CI 1.05, 3.16) were independently associated with cardiac rupture. Independent predictors of nonrupture death included age >70 years (OR 3.68; 95% CI 2.53, 5.35) and prior MI (OR 2.14; 95%, CI 1.45, 3.17). There was no association between the type of thrombin inhibition, the intensity of anticoagulation and cardiac rapture. CONCLUSIONS Cardiac rupture following thrombolytic therapy tends to occur in older patients and may explain the disproportionately high mortality rate among women in prior dinical trials. Unlike major hemorrhagic complications, there is no evidence that the intensity of anticoagulation associated with heparin or hirudin administration influences the occurrence of rupture