Faculty Bibliography

BACKGROUND: It is unclear whether abnormalities of arginine and nitric oxide metabolism are related to hemodynamic dysfunction and mortality in patients with cardiogenic shock (CS) after acute myocardial infarction. METHODS AND RESULTS: Plasma metabolites reflecting arginine bioavailability, nitric oxide metabolism, and protein oxidation were analyzed by mass spectrometry in patients with CS (n=79) and age- and gender-matched patients with coronary artery disease and normal left ventricular function (n=79). CS patients had higher levels of asymmetric dimethylarginine (ADMA; P<0.0001), symmetric dimethylarginine (P<0.0001), monomethylarginine (P=0.0003), nitrotyrosine (P<0.0001), and bromotyrosine (P<0.0001) and lower levels of arginine (P<0.0001), ratio of arginine to ornithine (P=0.03), and ratio of arginine to ornithine plus citrulline) (P=0.0003). CS patients with elevated ADMA levels were 3.5-fold (95% confidence interval, 1.4 to 11.3; P=0.02) more likely to die in 30 days than patients with low ADMA levels. ADMA remained the only independent predictor of mortality on multiple logistic regression analysis. In patients with normal renal function, symmetric dimethylarginine levels inversely correlated with mean arterial pressure and systemic vascular resistance, whereas levels of ADMA correlated with pulmonary capillary wedge pressure and both systolic and diastolic pulmonary artery pressures. Despite dramatic elevations, levels of protein oxidation products did not predict hemodynamic dysfunction or mortality in CS patients. CONCLUSIONS: CS is characterized by an arginine-deficient and highly specific pro-oxidant state, with elevated levels of methylated arginine derivatives, including endogenous nitric oxide synthase inhibitors. Levels of methylated arginine derivatives strongly correlate with hemodynamic dysfunction. Among all clinical and laboratory parameters monitored, ADMA levels were the strongest independent predictor of 30-day mortality

As of April 2007 the early open artery hypothesis is alive and well, but the late open artery hypothesis is adrift. For the foreseeable future, stable patients with persistent occlusion of the infarct artery late after myocardial infarction, and without severe ischaemia or uncontrollable angina, should be managed initially with optimal medical treatment alone, and not with percutaneous coronary intervention. Efforts should focus on establishing reperfusion earlier, including reducing the time to patient presentation

BACKGROUND: Women with acute myocardial infarction are more likely than men to experience reinfarction, bleeding, or death. This difference has been hypothesized to be due to older age, treatment delay, and comorbidities in women. Use of diagnostic and therapeutic modalities may also differ. There is controversy regarding whether female sex is an independent risk factor for death and/or bleeding. METHODS: The GUSTO (Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes) V Investigators studied standard-dose reteplase vs standard-dose abciximab plus half-dose reteplase in patients with myocardial infarction. RESULTS: Women were older and more often had diabetes mellitus and hypertension. Angiography and percutaneous coronary intervention were less frequent in women. Death (9.8% vs 4.4% at 30 days; odds ratio [OR], 2.00; 95% confidence interval, 1.59-2.53; P < .001) and bleeding (6.4% vs 2.5%; OR, 1.31; 95% confidence interval, 1.18-1.45; P < .01) were more common in women. There was no association between treatment assignment and death in either sex; bleeding was more common in both sexes receiving combination therapy. Female sex was independently associated with mortality. After Killip class greater than 1 (OR, 4.7), female sex (OR, 2.0) was the strongest correlate of death. Female sex was independently associated with bleeding for both treatments. CONCLUSIONS: Female sex is independently associated with death and bleeding complications among fibrinolytic-treated patients with myocardial infarction. There remains a sex differential in the use of angiography and, therefore, percutaneous coronary intervention after fibrinolysis. Further research will determine what mediates excess risk in women