Faculty Bibliography

AIMS: In acute myocardial infarction (AMI), baseline hyperglycaemia predicts adverse outcomes, but the relation between subsequent change in glucose levels and outcomes is unclear. We evaluated the prognostic significance of baseline glucose and the change in glucose in the first 24 h following AMI. METHODS AND RESULTS: We analysed 1469 AMI patients with baseline and 24 h glucose data from the CARDINAL trial database. Baseline glucose and the 24 h change in glucose (24 h glucose level subtracted from baseline glucose) were included in multivariable models for 30- and 180-day mortality. By 30 and 180 days, respectively, 45 and 74 patients had died. In the multivariable 30-day mortality model, neither baseline glucose nor the 24 h change in glucose predicted mortality in diabetic patients (n=250). However, in nondiabetic patients (n=1219), higher baseline glucose predicted higher mortality [hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.04-1.20, per 0.6 mmol/L increase], and a greater 24 h change in glucose predicted lower mortality (HR 0.91, 95% CI 0.86-0.96, for every 0.6 mmol/L drop in glucose in the first 24 h) at 30 days. Baseline glucose and the 24 h change in glucose remained significant multivariable mortality predictors at 180 days in nondiabetic patients. CONCLUSION: Both higher baseline glucose and the failure of glucose levels to decrease in the first 24 h after AMI predict higher mortality in nondiabetic patients

BACKGROUND: The role of diabetes mellitus (DM) in cardiogenic shock (CS) complicating an acute myocardial infarction (AMI) is not well understood. Previous studies have reported an in-hospital mortality rate for patients with DM and CS of about 60%. OBJECTIVES: This study compares the 1-year mortality rates of patients with DM and those without (NDM) and evaluates early revascularization (ERV) compared with initial medical stabilization (IMS) in patients with DM and CS. Methods: Baseline characteristics, clinical and hemodynamic measures, and management were compared for 90 patients (31%) with DM and 198 with NDM (69%) who were randomized to ERV or IMS in the SHOCK Trial. RESULTS: When compared with NDM, patients with DM were of similar age but had higher rates of prior MI (44.4 vs. 27.8%, p = 0.007) and hypertension (56.2 vs. 42.5%, p = 0.04). The DM group had a lower rate of fibrinolytic therapy (44.4 vs. 60.1%, p = 0.02). In patients randomized to ERV, patients with DM had a higher rate of coronary artery bypass grafting (CABG) (50.0 vs. 30.9%, p = 0.03) despite similar rates of triple-vessel disease. The 1-year mortality rates in both groups were equivalent (58.9%). One-year mortality was not associated with diabetes (hazard ratio [HR] 1.02, 95% CI, 0.73-1.42, p = 0.91). The benefit of an ERV strategy was similar (HR [DM] 0.62; HR [NDM] 0.75, p = 0.58). Even after adjusting for the imbalance in CABG rates, 1-year mortality was not associated with DM. CONCLUSION: Diabetes mellitus is not a predictor of 1-year mortality in CS after AMI. The benefit from an ERV strategy is similar for DM and NDM. The management strategies and influence of DM on mortality in CS deserve further evaluation

BACKGROUND: Left ventricular diastolic abnormalities are associated with adverse outcome in myocardial infarction. Intra-aortic balloon pump (IABP) support is associated with improved diastolic filling. In the SHOCK trial and registry, average left ventricular ejection fraction (LVEF) was approximately 30%, higher than expected based on the classic paradigm. We hypothesized that restrictive physiology plays a role in cardiogenic shock (CS). METHODS: Echocardiograms obtained during the SHOCK trial within 24 hours of randomization were centrally interpreted. Patients with quantifiable mitral E-wave deceleration time were included (n = 64). The restrictive filling pattern was defined as deceleration time < 140 milliseconds. RESULTS: The restrictive pattern was seen in 60.9% of patients studied. Patients with this pattern had lower LVEF (31.1% vs 39.0%, P = .02) and higher wall motion score index (2.1 vs 1.8, P = .05). Patients with restriction were more likely to have IABP support during echocardiography (73.7% vs 43.5%, P = .03). There was no difference with and without restriction in demographic and hemodynamic variables or in mitral regurgitation degree or extent of coronary disease. The restrictive pattern had positive predictive value of 80% for pulmonary capillary wedge pressure > or = 20 mm Hg. Thirty-day survival was 53.9% with restriction versus 68.0% without restriction, P = .31. There was no difference in New York Heart Association class at 1 year between groups. CONCLUSIONS: The restrictive filling pattern is common in patients with CS, which may suggest that diastolic dysfunction contributes to CS pathogenesis. Patients with the restrictive pattern had lower LVEF despite IABP support. An association between the restrictive pattern and mortality was not demonstrated; power was limited by sample size

AIMS: While natriuretic peptides have demonstrated diagnostic and prognostic potential in cardiac disorders, little is known about their relationship with the onset and quantification of myocardial infarction. The relationship of serial N-terminal pro-brain natriuretic peptide (NT-proBNP) with duration from symptom onset, infarct size and prognosis in ST elevation myocardial infarction (STEMI) patients treated with primary percutaneous intervention was examined. METHODS AND RESULTS: Three hundred thirty-one STEMI patients in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial, which evaluated pexelizumab versus placebo, were studied. NT-proBNP (pg/mL) was measured at randomization, 24 h and 72 h; creatine kinase-MB area under the curve was measured at 72 h; and QRS score was assessed at discharge. Prognosis was ascertained from the 90-day composite clinical outcome of death, shock, stroke and congestive heart failure. Multivariate logistical regression was used to adjust for baseline characteristics for models at randomization, 24 h and 72 h. NT-proBNP was higher in patients with longer time from symptom onset (P<0.001) and correlated with measures of infarct size, including the area under the curve (P<0.001) and QRS score (P<0.001). Patients reaching the primary end point had markedly higher NT-proBNP at each sampling period (P<0.001). NT-proBNP at all time points was the strongest independent predictor of the primary end point in the multivariate model: in the 24 h model, only age and 24 h NT-proBNP (C-index 0.83); and only age, Killip class and NT-proBNP was in the 72 h model (C-index 0.85). CONCLUSIONS: Higher NT-proBNP at 24 h correlated with larger infarct size and worse clinical outcomes. NT-proBNP at baseline, 24 h and 72 h after presentation with acute STEMI, is an independent predictor of a poor outcome and adds clinically useful prognostic information

BACKGROUND: The COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial previously demonstrated an unexpected dose-dependent reduction in 90-day mortality after bolus/infusion of pexelizumab despite no reduction in the primary end point of myocardial infarction (MI) size. We examined whether the mortality benefit was related to established modulators of clinical benefit such as baseline demographics, time to treatment from symptom onset, myocardial perfusion post-percutaneous coronary intervention (PCI), and extent of ST resolution. METHODS AND RESULTS: Eight hundred fourteen patients were randomized into 3 groups; (1) placebo, (2) pexelizumab bolus 2.0 mg/kg and placebo infusion for 20 hours, and (3) pexelizumab bolus 2.0 and 0.05 mg/kg per hour infusion for 20 hours commencing 4 hours after the bolus. Subjects presented with ST elevation MI within 6 hours of symptom onset and underwent PCI, creatine kinase (CK), and CK-MB measurements taken sequentially to define CK-MB area under the curve (AUC) and sequential ECG's defined ST resolution and QRS infarct size. Whereas mortality for both placebo and bolus pexelizumab groups rose during later time after presentation, it remained low and did not change appreciably during the 6-hour randomization window when patients received pexelizumab bolus infusion. Amplification of the mortality benefit was evident in patients with the highest quartile of hemodynamic compromise, that is, heart rate > or = 90 beat/min and systolic blood pressure < or = 118 mm Hg (3.2% vs 11.3% P = .004). A significant interaction between treatment assignment and hemodynamic status (P = .013) existed after adjusting for age, race, and MI location. Clinical benefit was not related to infarct size, extent of ST elevation, or evidence of angiographic or electrocardiographic reperfusion. CONCLUSIONS: These data raise the possibility that the clinical benefit of pexelizumab is mediated through novel pathways such as reduction in apoptosis or other mechanisms

AIMS: To determine clinical correlates and optimal treatment strategy in patients with cardiogenic shock (CS) on admission. METHODS AND RESULTS: In SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK? (SHOCK) trial and registry patients with left ventricular (LV) dysfunction (n=1053), CS on admission occurred in 26% of directly admitted patients (n=166/627). Time from myocardial infarction to CS was shorter, initial haemodynamic profile poorer, and aggressive treatment less frequent in CS on admission than in delayed CS patients. CS on admission patients constituted a smaller relative proportion (11%) of the transferred (n=48/426) when compared with the directly admitted cohort (P<0.001). In-hospital mortality was higher (75 vs. 56%; P<0.001) with more rapid death (24-h mortality 40 vs. 17%; P<0.001) in CS on admission than in delayed CS patients. Emergency revascularization reduced in-hospital mortality in CS on admission (60 vs. 82%; P=0.001) and in delayed CS patients similarly (46 vs. 62%; P<0.001; interaction P=0.25). After adjustment for clinical differences, CS on admission was an independent predictor of in-hospital mortality (P=0.008). CONCLUSION: CS on admission patients have a worse outcome but benefit equally from emergency revascularization as delayed CS patients, emphasizing the need for rapid and direct access of CS on admission patients to facilities providing this care

We sought to determine the frequency of electrocardiographic (ECG) acquisition within 10 minutes of hospital arrival, factors associated with delayed ECG acquisition, and any relation among delayed ECG acquisition, treatment patterns, and clinical outcomes. We therefore analyzed data from 63,478 patients (26,615 women, 42%) with high-risk non-ST-segment elevation acute coronary syndromes (designated by positive cardiac markers and/or ischemic ST-segment changes) who were enrolled in the CRUSADE Quality Improvement Initiative from February 2001 to March 2004. Patients were categorized based on time to electrocardiography as delayed (>10 minutes from hospital arrival) or nondelayed (<10 minutes). Multivariable predictors of delayed ECG acquisition were determined. Overall, median time to electrocardiography was 15 minutes (25th to 75th percentile 7 to 32). ECG acquisition was delayed (median 25 minutes, 25th to 75th percentile 16 to 50) in 41,397 patients (65.2%). In the remaining 34.8%, time to electrocardiography was <10 minutes (median 5 minutes, 25th to 75th percentile 3 to 8). Women were more likely than men to have delayed ECG acquisition (69% vs 62%), and female gender was the most significant predictor of delayed ECG acquisition (odds ratio 1.29, 95% confidence interval 1.25 to 1.34). In conclusion, only 33% of high-risk patients with non-ST-segment elevation acute coronary syndrome had an initial electrocardiogram obtained <10 minutes of arrival as recommended. Women were significantly more likely than men to have delayed ECG acquisition. Emergency departments should focus on decreasing the time to initial ECG acquisition to improve treatment of acute coronary syndrome in this group