Faculty Bibliography

PURPOSE: Obesity is a coronary disease risk factor, but its independent effect on clinical outcomes following acute coronary syndromes has not been quantified. We evaluated the relationship between elevated body mass index (BMI) and 30-day, 90-day, and 1-year clinical outcomes postacute coronary syndromes. SUBJECTS AND METHODS: Using 15 071 patients (normal weight [BMI = 18.5-24.9 kg/m(2)], overweight [BMI = 25-29.9 kg/m(2)], obese [BMI = 30-34.9 kg/m(2)] or very obese [BMI > or =35 kg/m(2)]) randomized from 1997-1999 in the SYMPHONY (Sibrafiban vs aspirin to Yield Maximum Protection from ischemic Heart events postacute cOroNary sYndromes) and 2nd SYMPHONY trials, we evaluated the relationships between BMI and 30-day, 90-day, and 1-year mortality and 30-day and 90-day death or myocardial infarction. RESULTS: Increasing BMI was associated with younger age, multiple comorbidities, and greater cardiac medication and procedure use; however, systolic function and coronary disease extent were similar for all BMI categories. Unadjusted Kaplan-Meier mortality estimates were higher for normal-weight patients than for all other BMI groups. After multivariable adjustment, the 30-day mortality hazard ratios (95% confidence interval [CI]) were: overweight, 0.66 (95% CI: 0.47 to 0.94); obese, 0.61 (95% CI: 0.39 to 0.97); very obese, 0.89 (95% CI: 0.48 to 1.64). Adjusted hazard ratios were similar for 90-day and 1-year mortality. There were no statistically significant differences among BMI groups in 30-day and 90-day death or myocardial infarction (unadjusted or adjusted). CONCLUSION: Overweight and obese BMI classifications were associated with better intermediate-term survival after acute coronary syndromes than normal weight and very obese, but death or myocardial infarction rates were similar. Further study is required to understand the apparent association of overweight and moderate obesity with better intermediate-term outcomes

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

CONTEXT: Early mechanical revascularization in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock is a therapeutic strategy that reduces mortality. It has been a class I recommendation in guidelines from the American College of Cardiology and the American Heart Association since 1999 for patients younger than 75 years. However, little is known about implementation of these guidelines in practice. OBJECTIVES: To assess trends in early revascularization and mortality for patients with cardiogenic shock complicating AMI and to determine whether the national guidelines affect revascularization rates. DESIGN, SETTING, AND PATIENTS: Prospective, observational study of 293,633 patients with ST-elevation myocardial infarction (25,311 [8.6%] had cardiogenic shock; 7356 [29%] had cardiogenic shock at hospital presentation) enrolled in the National Registry of Myocardial Infarction (NRMI) from January 1995 to May 2004 at 775 US hospitals with revascularization capability (defined as the capability to perform cardiac catheterization, percutaneous coronary intervention [PCI], and open-heart surgery). MAIN OUTCOME MEASURES: Management patterns and in-hospital mortality rates. RESULTS: There was an increase in primary PCI rates from 27.4% to 54.4% (P<.001) in hospitals with revascularization capability that paralleled the change in PCI for ST-elevation myocardial infarction. There was no significant change in rates of immediate coronary artery bypass graft surgery (from 2.1% to 3.2%). Propensity-adjusted multivariable analyses demonstrated that primary PCI was associated with a decreased odds of death during hospitalization (odds ratio, 0.46; 95% confidence interval, 0.40-0.53). There were no differences in the rates of change in revascularization rates based on the date when the guidelines were released regardless of patient age. Overall in-hospital cardiogenic shock mortality decreased from 60.3% in 1995 to 47.9% in 2004 (P<.001). CONCLUSIONS: The use of PCI for patients with cardiogenic shock was associated with improved survival in a large group of hospitals with revascularization capability. The American College of Cardiology and American Heart Association guidelines had no detectable temporal impact on revascularization rates. These findings support the need for increased adherence to these guidelines

BACKGROUND: The role of inflammation in patients with coronary artery disease is emerging. We sought to assess the profile and outcomes of patients with a clinical syndrome of severe systemic inflammation that led to a diagnosis of suspected sepsis in the setting of acute myocardial infarction complicated by cardiogenic shock (CS). METHODS: Patients enrolled in the randomized SHOCK (SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK) trial (n = 302) were divided into those with clinical signs of severe systemic inflammation (eg, fever [94%] or leukocytosis [72%]) that led to a diagnosis of suspected sepsis (n = 54 [18%]) and those without suspected sepsis (controls; n = 243 [80%]). The patients with suspected sepsis were then further subdivided into those who were considered to be potentially infectious (positive culture result ['culture-positive']; n = 40) and those who were not (negative culture result ['culture-negative']; n = 14). RESULTS: Severe systemic inflammation was diagnosed 4 and 2 days after the onset of CS in culture-positive and culture-negative patients, respectively. Patients who developed systemic inflammation tended to be younger (P = .05) and to have lower systemic vascular resistance (SVR) near the onset of CS (P = .006). Many culture-positive patients (40%) had undergone coronary artery bypass graft surgery. However, the lower the initial SVR, the higher the risk of developing culture-positive systemic inflammation (P = .01), even after controlling for age and coronary artery bypass graft surgery. A time-dependent model, adjusted for age, showed that culture-positive patients were at significantly higher risk for death than were controls (hazard ratio, 2.22; 95% confidence interval, 1.32-3.76; P = .008). CONCLUSIONS: Almost one fifth of patients with acute myocardial infarction complicated by CS showed clinical signs of severe systemic inflammation, and those who were culture-positive for sepsis had twice the risk of death. The observation of lower SVR at the onset of shock in patients who subsequently had culture-positive systemic inflammation suggests that inappropriate vasodilation may play an important role in the pathogenesis and persistence of shock and in the risk of infection

OBJECTIVES: Our goal was to describe the functional status of cardiogenic shock survivors, identify the correlates of cardiogenic shock, and compare global quality of life and functional status of patients randomly assigned to treatment with emergency revascularization (ERV) versus initial medical stabilization (IMS). BACKGROUND: Historically, the hospital survival rate of patients with cardiogenic shock complicating acute myocardial infarction (MI) has been very low. Shock survivors are salvaged from a critically ill state, and their later functional status is not well documented. The SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK (SHOCK) trial showed significantly improved one-year survival after ERV compared with IMS. METHODS: The SHOCK trial survivors completed interviews at 2 weeks after discharge and at 6 and 12 months after MI. Functional status assessment included the Multidimensional Index of Life Quality and New York Heart Association (NYHA) congestive heart failure functional class. RESULTS: Eighty-seven percent of one-year survivors of the SHOCK trial were in NYHA functional class I or II. Between two weeks after discharge and one year after MI, improvement was similar in the two treatment groups (18% overall), but fewer patients remained stable (44% vs. 71%), and more patients worsened or died (34% vs. 15%) in the IMS group compared with those assigned to ERV. Assignment to ERV was the only independent predictor of outcome at one year. CONCLUSIONS: Although one-year mortality after ERV is still high (54%), most survivors have good functional status. The ERV patients have a lower rate of deterioration than IMS patients. The level of recovery for shock patients undergoing ERV is similar to that of historical controls not in cardiogenic shock undergoing elective revascularization

BACKGROUND: We studied the potential interaction between baseline risk of death and treatment with either standard fibrinolytic monotherapy or combination fibrin and platelet lysis with respect to outcome of patients with ST-elevation myocardial infarction (STEMI) enrolled in the Global Utilization of Strategies To open Occluded arteries (GUSTO) V trial. METHODS: Using the Thrombolysis in Myocardial Infarction (TIMI) risk score (0-14 points) for STEMI, we analyzed the 30-day and 1-year mortality according to treatment assignment and risk category. Multivariable analysis was performed to identify the potential interactions between treatment and baseline risk. RESULTS: The TIMI risk score could be calculated in 16256 patients (98% of patients enrolled). The median score was 2 (1-4) in each treatment group (P = .07). The risk score was significantly associated with 30-day mortality (hazard ratio [HR], 1.52; 95% CI 1.47-1.56, P < .001, for each additional 1 point), as well as with 1-year mortality (HR 1.51, CI 1.47-1.55, P < .001). The treatment allocation was not significantly related to mortality, and there was no significant interaction between baseline risk score and treatment with respect to either end point. Although combination therapy significantly reduced death or reinfarction at 7 days (HR 0.69, CI 0.54-0.89, P < .01), independent of the risk score, there was no significant statistical interaction between the two (P = .29). CONCLUSION: The TIMI risk score accurately predicted early and 1-year mortality in patients with STEMI treated with pharmacological reperfusion. We did not identify any heterogeneity in the response of patients to combination therapy according to their TIMI risk score

BACKGROUND: In the SHOCK trial, the group of patients aged >or=75 years did not appear to derive the mortality benefit from early revascularization (ERV) versus initial medical stabilization (IMS) that was seen in patients aged <75 years. We sought to determine the reason for this finding by examining the baseline characteristics and outcomes of the 2 treatment groups by age. METHODS: Patients with cardiogenic shock (CS) secondary to left ventricular (LV) failure were randomized to ERV within 6 hours or to a period of IMS. We compared the characteristics by treatment group of patients aged >or=75 years and of their younger counterparts. RESULTS: Of the 56 enrolled patients aged >or=75 years, those assigned to ERV had lower LV ejection fraction at baseline than IMS-assigned patients (27.5% +/- 12.7% vs 35.6% +/- 11.6%, P = .051). In the elderly ERV and IMS groups, 54.2% and 31.3%, respectively, were women ( P = .105) and 62.5% and 40.6%, respectively, had an anterior infarction (P = .177). The 30-day mortality rate in the ERV group was 75.0% in patients aged >or=75 years and 41.4% in those aged <75 years. In the IMS group, 30-day mortality was 53.1% for those aged >or=75 years, similar to the 56.8% for patients aged <75 years. CONCLUSIONS: Overall, the elderly randomized to ERV did not have better survival than elderly IMS patients. Despite the strong association of age and death post-CS, elderly patients assigned to IMS had a 30-day mortality rate similar to that of IMS patients aged <75 years, suggesting that this was a lower-risk group with more favorable baseline characteristics. The lack of apparent benefit from ERV in elderly patients in the SHOCK trial may thus be due to differences in important baseline characteristics, specifically LV function, and play of chance arising from the small sample size. Therefore, the SHOCK trial overall finding of a 12-month survival benefit for ERV should be viewed as applicable to all patients, including those >or=75 years of age, with acute myocardial infarction complicated by CS

OBJECTIVE: To determine the characteristics and prognostic importance of right ventricular (RV) dilatation and dysfunction in patients with cardiogenic shock secondary to left ventricular (LV) dysfunction enrolled in the Should we emergently revascularize occluded coronaries for cardiogenic shock (SHOCK) trial. METHODS: LV and RV size and function were quantified by echocardiography in 99 patients with cardiogenic shock secondary to predominant LV dysfunction. RESULTS: For all patients, RV dysfunction was not associated with a poor 1-year survival. When the 59 patients with RV dysfunction were stratified into two morphologic groups based upon LV-to-RV end-diastolic area ratio (LV/RV) < or >or=2, the presence of disproportionate RV enlargement (LV/RV <2) was associated with inferior myocardial infarction (80%) and right coronary artery culprit disease (79%). In contrast, the index myocardial infarction in patients with predominant LV enlargement (LV/RV >or=2) was anterior (69%) and associated with left anterior descending artery disease (64%). Patients with LV/RV <2 had significantly higher right atrial pressures (20.1+/-5.2 compared with 14.5+/-8.9 mmHg, P=0.001) and lower RV fractional area change (20.4+/-8.7 compared with 33.5+/-11.0%, P=0.0001), heart rate (87+/-21 compared with 106+/-23 beats/min, P=0.006) and cardiac index (1.5+/-0.5 compared with 2.0 +/-0.9 l/min per m, P=0.007) than patients with LV/RV >or=2. Despite the hemodynamic profile and severity of RV dysfunction in the LV/RV <2 group, 12-month survival was significantly greater in these patients (70% LV/RV <2 compared with 34% LV/RV >or=2, P=0.027). CONCLUSIONS: In patients with cardiogenic shock secondary to predominant LV failure, the presence of RV dilatation and dysfunction identifies a subgroup of patients with predominant inferior myocardial infarction and an improved long-term prognosis

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