Faculty Bibliography

AIMS: To evaluate the relationship between activated partial thromboplastin time (aPTT) and clinical outcomes in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-V) trial comparing standard-dose reteplase to half-dose reteplase and abciximab. METHODS AND RESULTS: We analysed data on 11,420 patients receiving unfractionated heparin. Peak aPTT levels recorded during the hospitalization were correlated with clinical outcomes. Multivariable logistic regression models examined the relationship between peak aPTT levels and (i) moderate-to-severe bleeding, (ii) intracerebral haemorrhage, (iii) reinfarction, and (iv) 30-day mortality. Non-linear relationships were explored in the models using cubic spline functions. Higher rates of significant complications were seen in both groups when aPTT levels were <50 s or when levels were >70 s. In the combination therapy group, the relationship between aPTT levels and bleeding appeared accentuated. Reinfarction rates increased gradually as aPTT levels were >70 s in both groups, but the relationships were not statistically significant. Peak aPTT levels <50 s were associated with increased 30-day mortality even after multivariable adjustment. CONCLUSION: Peak aPTT levels <50 s and >70 s are associated with worse clinical outcomes in the modern era of fibrinolytic therapy; these relationships are different in patients receiving standard reteplase vs. combination therapy

OBJECTIVES: We hypothesized that significant disparities in gender exist in the management of patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). BACKGROUND: Gender-related differences in the diagnosis and treatment of ACS have important healthcare implications. No large-scale examination of these disparities has been completed since the publication of the revised American College of Cardiology/American Heart Association guidelines for management of patients with NSTE ACS. METHODS: Using data from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative, we examined differences of gender in treatment and outcomes among patients with NSTE ACS. RESULTS: Women (41% of 35,875 patients) were older (median age 73 vs. 65 years) and more often had diabetes and hypertension. Women were less likely to receive acute heparin, angiotensin-converting enzyme inhibitors, and glycoprotein IIb/IIIa inhibitors and less commonly received aspirin, angiotensin-converting enzyme inhibitors, and statins at discharge. The use of cardiac catheterization and revascularization was higher in men, but among patients with significant coronary disease, percutaneous revascularization was performed in a similar proportion of women and men. Women were at higher risk for unadjusted in-hospital death (5.6% vs. 4.3%), reinfarction (4.0% vs. 3.5%), heart failure (12.1% vs. 8.8%), stroke (1.1% vs. 0.8%), and red blood cell transfusion (17.2% vs. 13.2%), but after adjustment, only transfusion was higher in women. CONCLUSIONS: Despite presenting with higher risk characteristics and having higher in-hospital risk, women with NSTE ACS are treated less aggressively than men

White blood cell (WBC) count and temperature are 2 global measures of inflammation that are systematically gathered and easily identifiable in a clinical setting, unlike many other markers of inflammation being investigated in patients with coronary artery disease. The prognostic usefulness of the WBC count and temperature were evaluated in a large acute myocardial infarction trial, the Complement And ReDuction of INfarct size after Angioplasty or Lytics program. Baseline and serial measurements of WBC counts and temperature were correlated with infarct size and clinical outcome

CONTEXT: Enoxaparin has demonstrated advantages over unfractionated heparin in low- to moderate-risk patients with non-ST-segment elevation acute coronary syndromes (ACS) treated with a conservative strategy. OBJECTIVES: To compare the outcomes of patients treated with enoxaparin vs unfractionated heparin and to define the role of enoxaparin in patients with non-ST-segment elevation ACS at high risk for ischemic cardiac complications managed with an early invasive approach. DESIGN, SETTING, AND PARTICIPANTS: The Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial was a prospective, randomized, open-label, multicenter, international trial conducted between August 2001 and December 2003. A total of 10 027 high-risk patients with non-ST-segment elevation ACS to be treated with an intended early invasive strategy were recruited. INTERVENTIONS: Subcutaneous enoxaparin (n = 4993) or intravenous unfractionated heparin (n = 4985) was to be administered immediately after enrollment and continued until the patient required no further anticoagulation, as judged by the treating physician. MAIN OUTCOME MEASURES: The primary efficacy outcome was the composite clinical end point of all-cause death or nonfatal myocardial infarction during the first 30 days after randomization. The primary safety outcome was major bleeding or stroke. RESULTS: The primary end point occurred in 14.0% (696/4993) of patients assigned to enoxaparin and 14.5% (722/4985) of patients assigned to unfractionated heparin (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.86-1.06). No differences in ischemic events during percutaneous coronary intervention (PCI) were observed between enoxaparin and unfractionated heparin groups, respectively, including similar rates of abrupt closure (31/2321 [1.3%] vs 40/2364 [1.7%]), threatened abrupt closure (25/2321 [1.1%] vs 24/2363 [1.0%]), unsuccessful PCI (81/2281 [3.6%] vs 79/2328 [3.4%]), or emergency coronary artery bypass graft surgery (6/2323 [0.3%] vs 8/2363 [0.3%]). More bleeding was observed with enoxaparin, with a statistically significant increase in TIMI (Thrombolysis in Myocardial Infarction) major bleeding (9.1% vs 7.6%, P =.008) but nonsignificant excess in GUSTO (Global Utilization of Streptokinase and t-PA for Occluded Arteries) severe bleeding (2.7% vs 2.2%, P =.08) and transfusions (17.0% vs 16.0%, P =.16). CONCLUSIONS: Enoxaparin was not superior to unfractionated heparin but was noninferior for the treatment of high-risk patients with non-ST-segment elevation ACS. Enoxaparin is a safe and effective alternative to unfractionated heparin and the advantages of convenience should be balanced with the modest excess of major bleeding

BACKGROUND: We evaluated whether the use of glycoprotein IIb/IIIa receptor inhibitors, in addition to heparin and aspirin, imparts an incremental benefit in a subgroup of patients with acute coronary syndromes (ACS) who had congestive heart failure (CHF) symptoms at presentation. METHODS: We analyzed patients enrolled in the Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, a randomized, double-blind, placebo-controlled study evaluating the use of eptifibatide versus placebo for patients with ACS without persistent ST-elevation. We compared the clinical characteristics and 30-day outcomes for 861 patients who had Killip class II or III CHF symptoms with those of 8558 patients who had no CHF symptoms. RESULTS: Odds ratios for the primary end point, 30-day death or non-fatal myocardial infarction, in the placebo group versus the eptifibatide group were similar for patients with and without CHF (odds ratio, 1.11; 95% CI, 0.8-1.5; odds ratio, 1.13; 95% CI, 1.0-1.3). However, adverse events were almost twice as frequent for patients with CHF compared with patients with no CHF (24.5% vs 14%). CONCLUSIONS: Although patients with non-ST-segment elevation ACS who have CHF have markedly worse outcomes than patients without CHF symptoms, we did not find an incremental benefit from the use of eptifibatide in this seriously ill subgroup

In a nonrandomized feasibility study of therapeutic hypothermia in acute myocardial infarction, 18 patients were treated with endovascular cooling (Alsius, Irvine, California) as adjunctive therapy to primary percutaneous coronary intervention to assess measures of infarct size (area under the curve creatinine kinase-MB and technetium-99m single-photon emission computed tomography sestamibi) and the quality of myocardial perfusion (continuous ST-segment monitoring). Periprocedural endovascular cooling successfully decreased core body temperature (median 33.5 degrees C) and was well tolerated, which supports the evaluation of adjunctive hypothermia in pivotal trials to limit infarct size and decrease reperfusion injury

BACKGROUND: Diabetes is associated with an increased risk for coronary artery disease (CAD) and its complications. The relative effect of glucose-lowering strategies of 'insulin provision' versus 'insulin sensitization' among patients with CAD remains unclear. METHODS: To evaluate the associations of diabetes and hypoglycemic strategies with clinical outcomes after acute coronary syndromes, we analyzed data from 15,800 patients enrolled in the SYMPHONY and 2nd SYMPHONY trials. RESULTS: Compared with nondiabetic patients, patients with diabetes (n = 3101; 19.6%) were older, more often female, more often had prior CAD, hypertension, and hyperlipidemia, and less often were current smokers. The diabetic cohort had higher 90-day unadjusted risk of the composite of death/myocardial infarction (MI)/severe recurrent ischemia (SRI), death/MI, and death alone, as well as a near doubling of 1-year mortality rates. At 1 year, diabetes was associated with significantly higher adjusted risks of death/MI/SRI (OR, 1.3 [95% confidence interval, 1.1, 1.5]) and death/MI (OR, 1.2 [1.0, 1.4]). Hypoglycemic therapy including only insulin and/or sulfonylurea (insulin-providing; n = 1473) was associated with higher 90-day death/MI/SRI compared with therapy that included only biguanide and/or thiazolidinedione therapy (insulin-sensitizing; n = 100) (12.0% vs 5.0%); (adjusted OR, 2.1 [1.2, 3.7]). CONCLUSIONS: Diabetic patients with acute coronary syndromes had worse clinical outcomes. Although the findings regarding the influence of glycemic-control strategies should be interpreted with caution because of the exploratory nature of the analyses and the relatively small sample size of the insulin-sensitizing group, the improved risk-adjusted outcomes associated with insulin-sensitizing therapy underscore the need to further evaluate treatment strategies for patients with diabetes and CAD

OBJECTIVES: We sought to analyze clinical, angiographic, and outcome correlates of hemodynamic parameters in cardiogenic shock. BACKGROUND: The significance of right heart catheterization in critically ill patients is controversial, despite the prognostic importance of the derived measurements. Cardiac power is a novel hemodynamic parameter. METHODS: A total of 541 patients with cardiogenic shock who were enrolled in the SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK (SHOCK) trial registry were included. Cardiac power output (CPO) (W) was calculated as mean arterial pressure x cardiac output/451. RESULTS: On univariate analysis, CPO, cardiac power index (CPI), cardiac output, cardiac index, stroke volume, left ventricular work, left ventricular work index, stroke work, mean arterial pressure, systolic and diastolic blood pressure (all p < 0.001), coronary perfusion pressure (p = 0.002), ejection fraction (p = 0.013), and pulmonary artery systolic pressure (p = 0.047) were associated with in-hospital mortality. In separate multivariate analyses, CPO (odds ratio per 0.20 W: 0.60 [95% confidence interval, 0.44 to 0.83], p = 0.002; n = 181) and CPI (odds ratio per 0.10 W/m(2): 0.65 [95% confidence interval, 0.48 to 0.87], p = 0.004; n = 178) remained the strongest independent hemodynamic correlates of in-hospital mortality after adjusting for age and history of hypertension. There was an inverse correlation between CPI and age (correlation coefficient: -0.334, p < 0.001). Women had a lower CPI than men (0.29 +/- 0.11 vs. 0.35 +/- 0.15 W/m(2), p = 0.005). After adjusting for age, female gender remained associated with CPI (p = 0.032). CONCLUSIONS: Cardiac power is the strongest independent hemodynamic correlate of in-hospital mortality in patients with cardiogenic shock. Increasing age and female gender are independently associated with lower cardiac power