Faculty Bibliography

BACKGROUND: The ideal revascularization strategy (bypass surgery versus percutaneous coronary intervention [PCI]) for patients with cardiogenic shock in the setting of left main coronary artery disease is unknown. METHODS: The Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock Trial and Registry included 164 patients with left main disease who underwent revascularization. Although the standard of care at the time and the trial protocol recommended coronary artery bypass graft surgery for patients with left main disease, the revascularization strategy (79 coronary artery bypass graft surgery and 85 PCI) was individualized for each patient by site investigators. RESULTS: The median time from myocardial infarction to revascularization was 24.3 hours (interquartile range, 8.7 to 82.5 hours) in the surgical group and 7.4 hours (interquartile range, 3.7 to 19.5 hours) in the PCI group (p < 0.05). Overall 30-day survival with surgery in this setting was 54% (95% confidence interval, 0.43 to 0.69) and was significantly superior to the 14% (95% confidence interval, 0.09 to 0.35) in the PCI group (p <or= 0.001). When the left main was the infarct-related artery, the 30-day survival rate was 40% in the surgical group (n = 6) and 16% in the PCI group (n = 15; p = 0.03). Coronary artery bypass graft surgery (hazard ratio, 0.41; 95% confidence interval, 0.22 to 0.77; p = 0.006) and age (per 10 years, hazard ratio, 1.04; 95% confidence interval, 1.01 to 1.08; p = 0.02) were independently associated with 30-day survival. CONCLUSIONS: Coronary artery bypass graft surgery appeared to provide a survival advantage over PCI at 30-day follow-up in patients with left main coronary artery disease. The impact of current PCI strategies on this subgroup is undetermined

OBJECTIVE: To evaluate the distribution and determinants of myocardial perfusion grade (MPG) following late recanalization of persistently occluded infarct-related arteries (IRA). BACKGROUND: MPG reflects microvascular integrity. It is an independent prognostic factor following myocardial infarction, but has been studied mainly in the setting of early reperfusion. The occluded artery trial (OAT) enrolled stable patients with persistently occluded IRAs beyond 24 hr and up to 28 days post-MI. METHODS: Myocardial blush was assessed using TIMI MPG grading in 261 patients with TIMI 3 epicardial flow following IRA PCI. Patients demonstrating impaired (0-1) versus preserved (2-3) MPG were compared with regard to baseline clinical and pre-PCI angiographic characteristics. RESULTS: Impaired MPG was observed in 60 of 261 patients (23%). By univariate analysis, impaired MPG was associated with failed fibrinolytic therapy, higher heart rate, lower systolic blood pressure, lower ejection fraction, LAD occlusion, absence of collaterals (P < 0.01) and ST elevation MI, lower diastolic blood pressure, and higher systolic sphericity index (P < 0.05). By multivariable analysis, higher heart rate, LAD occlusion, absence of collaterals and higher systolic sphericity index (P < 0.01), and lower systolic blood pressure (P < 0.05) were independently associated with impaired MPG. CONCLUSION: Preserved microvascular integrity was present in a high proportion of patients following late recanalization of occluded IRAs post-MI. Presence of collaterals was independently associated with preserved MPG and likely accounted for the high frequency of preserved myocardial perfusion in this clinical setting. Impaired MPG was associated with baseline clinical and angiographic features consistent with larger infarct size

OBJECTIVES: To determine predictors of outcome and examine the influence of baseline risk on therapeutic impact of late mechanical opening of a persistently occluded infarct related artery (IRA) after myocardial infarction (MI) in stable patients. BACKGROUND: Previous studies in patients with acute coronary syndromes suggest that the impact of IRA recanalization on clinical outcome is greatest in patients at highest risk. METHODS: Of 2201 patients (age 58.6+/-11.0) with IRA occlusion on days 3 to 28 after MI in the Occluded Artery Trial (OAT), 1101 were assigned to PCI and 1100 to medical therapy alone, and followed for a mean of 3.2 years. The primary end point was a composite of death, reinfarction, or NYHA class IV heart failure. Interaction of treatment effect with tertiles of predicted survival were examined using the Cox survival model. RESULTS: The 5-year rate for the primary endpoint was 18.9% versus 16.1% for patients assigned PCI and medical treatment alone (MED) respectively (HR=1.14;95% CI:0.92-1.43, p=0.23). Lack of benefit of PCI was consistent across the risk spectrum for both the primary endpoint and total mortality, including for the highest tertile (33.9% PCI versus 27.3 % MED, HR=1.27;99% CI:0.87-1.85 primary endpoint and 23.5% PCI versus 21.7% MED, HR=1.16,99% CI: 0.73-1.85 mortality). The independent predictors of the composite outcome were: history of heart failure (HR=2.06,p<0.001), peripheral vascular disease (HR=1.93,p=0.001), diabetes (HR=1.49,p=0.002), rales (HR=1.88,p<0.001), decreasing: ejection fraction (HR=1.48 per 10%,p<0.001), days from MI to randomization (HR=1.04 per day,p<0.001), and glomerular filtration rate (HR=1.11 per 10mL/min/1.73m(2),p<0.001). CONCLUSIONS: In OAT, there was no variation in the effect of PCI on clinical outcomes at different levels of patient risk, including the subset with very high event rates

BACKGROUND: Evidence suggests that both selective cyclooxygenase (COX)-2 inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of cardiovascular events. However, evidence from prospective studies of currently available COX-2 inhibitors and non-selective NSAIDs is lacking in patients at high cardiovascular risk who are taking aspirin. OBJECTIVE: To determine the cardiovascular outcomes in high risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib. METHODS: The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) of 18 325 patients with osteoarthritis comprised two parallel substudies, comparing lumiracoxib (COX-2 inhibitor) with either ibuprofen or naproxen. A post hoc analysis by baseline cardiovascular risk, treatment assignment, and low-dose aspirin use was performed. The primary composite end point was cardiovascular mortality, non-fatal myocardial infarction, and stroke at 1 year; a secondary end point was the development of congestive heart failure (CHF). RESULTS: In high risk patients among aspirin users, patients in the ibuprofen substudy had more primary events with ibuprofen than lumiracoxib (2.14% vs 0.25%, p = 0.038), whereas in the naproxen substudy rates were similar for naproxen and lumiracoxib (1.58% vs 1.48%, p = 0.899). High risk patients not taking aspirin had fewer primary events with naproxen than with lumiracoxib (0% vs 1.57%, p = 0.027), but not for ibuprofen versus lumiracoxib (0.92% vs 0.80%, p = 0.920). Overall, CHF developed more often with ibuprofen than lumiracoxib (1.28% vs 0.14%; p = 0.031), whereas no difference existed between naproxen and lumiracoxib. CONCLUSIONS: These data suggest that ibuprofen may confer an increased risk of thrombotic and CHF events relative to lumiracoxib among aspirin users at high cardiovascular risk. The study indicates that naproxen may be associated with lower risk relative to lumiracoxib among non-aspirin users. This study is subject to inherent limitations, and therefore should be interpreted as a hypothesis-generating study.

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