Faculty Bibliography

BACKGROUND: Little is known about predictors of survival in patients with persistent shock following acute myocardial infarction (MI) despite a patent infarct artery. METHODS: We examined data from TRIUMPH, a multicenter randomized clinical trial of the nitric oxide synthase inhibitor, L-N(G)-monomethyl-arginine, in patients with persistent vasopressor-dependent cardiogenic shock complicating acute MI at least 1 hour after established infarct-related artery patency. Patients who died within 30 days were compared with those who survived. Continuous variables were assessed using the Wilcoxon rank sum and categorical variables using the chi(2) test. Prespecified baseline variables were included in a multivariable logistic regression model to predict mortality. A second model incorporating baseline vasopressors and dosages and a third model including change in systolic blood pressure at 2 hours were also developed. Bootstrapping was used to assess the stability of model variables. RESULTS: Of 396 patients, 180 (45.5%) died within 30 days. Systolic blood pressure (SBP), measured on vasopressor support, and creatinine clearance were significant predictors of mortality in all models. The number of vasopressors and norepinephrine dose were also predictors of mortality in the second model, but the latter was no longer significant when change in SBP at 2 hours was added as a covariate in the third model. CONCLUSIONS: The SBP, creatinine clearance, and number of vasopressors are significant predictors of mortality in patients with persistent vasopressor-dependent cardiogenic shock following acute MI despite a patent infarct artery. These prognostic variables may be useful for risk-stratification and in selecting patients for investigation of additional therapies

BACKGROUND: Women with non-ST-segment elevation myocardial infarction (NSTEMI) who undergo coronary angiography have no obstructive coronary lesions more often than men. Sex-specific characteristics and outcomes of patients without obstructive coronary artery disease (CAD) have not been described previously. METHODS: Using data from NSTEMI patients enrolled in CRUSADE from 2001 to 2005, we evaluated differences in clinical features and in-hospital outcomes between men and women with no obstructive CAD. RESULTS: After excluding patients with missing catheterization and sex data (n = 1,494), previous coronary artery bypass grafting or percutaneous coronary intervention (47,907), catheterization contraindications (n = 6,588), and missing obstructive CAD status (n = 1,565), there were 55,514 patients (68.4%) with NSTE acute coronary syndromes (ACS) who underwent angiography (among women, 62.1% [21,294/34,290], and among men, 73% [34,220/46,875]; P < .001). Among these, a total of 5,538 patients (10.0%) had nonnonobstructive CAD-15.1% (3,221/21,294) of women and 6.8% (2,317/34,220) of men (P < .0001). In patients without obstructive CAD, women were as likely as men to have MI (troponin elevation in 89% vs 87%, P = .37). Women and men were equally likely to have larger troponin elevations (58.9% vs 58.6% with troponin >5x upper limit of normal, P = .69, respectively). In NSTEMI patients without obstructive CAD, in-hospital death (0.6% women vs 0.7% men) and cardiogenic shock (1.0% women vs 0.7% men) were infrequent. CONCLUSIONS: Among NSTE ACS patients undergoing coronary angiography, absence of obstructive CAD is more common in women than men. Although nonobstructive CAD was twice as common among women with NSTEMI, sex differences in characteristics and outcomes were similar to those found with obstructive CAD. Unadjusted in-hospital outcomes of NSTEMI patients with nonobstructive CAD are favorable in both sexes. Whether the underlying pathophysiology of NSTE ACS without documentation of obstructive CAD is different between women and men requires further study

BACKGROUND: We analyzed a prespecified hypothesis of the Occluded Artery Trial (OAT) that late percutaneous coronary intervention (PCI) of the infarct-related artery (IRA) would be most beneficial for patients with anterior myocardial infarction (MI). METHODS: Two thousand two hundred one stable, high-risk patients with total occlusion of the IRA (793 left anterior descending [LAD]) on days 3 to 28 (minimum of 24 hours) after MI were randomized to PCI and stenting with optimal medical therapy (1,101 patients) or to optimal medical therapy alone (1,100 patients). The primary end point was a composite of death, recurrent MI, or hospitalization for class IV heart failure. RESULTS: The 5-year cumulative primary end point rate was more frequent in the LAD group (19.5%) than in the non-LAD group (16.4%) (HR 1.34, 99% CI 1.00-1.81, P = .01). Within the LAD group, the HR for the primary end point in the PCI group (22.7%) compared with the medical therapy group (16.4%) was 1.35 (99% CI 0.86-2.13, P = .09), whereas in the non-LAD group the HR for the primary end point in PCI (16.9%) compared with medical therapy (15.8%) was 1.03 (99% CI 0.70-1.52, P = .83) (interaction P = .24). The results were similar when the effect of PCI was assessed in patients with proximal LAD occlusion. CONCLUSIONS: In stable patients, persistent total occlusion of the LAD post MI is associated with a worse prognosis compared with occlusion of the other IRAs. A strategy of PCI of occluded LAD IRA >24 hours post MI in stable patients is not beneficial and may increase risk of adverse events in comparison to optimal medical treatment alone

Purpose: The mechanisms underlying premature atherosclerosis in SLE are not understood. The endothelium merits focus since it provides the physiologic boundary which limits extravasation and diapedesis of inflammatory cells. Methods: One hundred and nineteen patients with SLE, predominantly non-Caucasian, and 71 healthy controls matched for age, sex and race, underwent carotid ultrasonography and donated blood for evaluation of circulating endothelial cells (CEC), soluble endothelial protein C receptor (sEPCR) and gene polymorphism at A6936G, soluble E-selectin, and adiponectin. Results: Carotid plaque was more prevalent among patients than controls (43% vs 17%, p=0.0002). Mean CCA IMT was greater in patients compared to controls (0.59mm+/-0.19 vs 0.54mm+/-0.11, p=0.03). Levels of CEC (19 vs 3 CECs/mL, p<0.0001) and sE-selectin (64 vs 36 ng/ml, p<0.0001) were significantly elevated in patients compared to controls. Unexpectedly, adiponectin was also significantly higher in patients compared to controls (16 ug/mL versus 11 ug/mL, p=0.0001) but no differences were seen in the levels of sEPCR or the distribution of genotype. Independent predictors of plaque status using logistic regression models included: age (p<0.0001; OR=2.1 per 10 year increase; 95% CI: 1.5-3.0), SLE status (p=0.015; OR=3.4 for SLE vs control; 95% CI: 1.3-9.1), sE-selectin (p=0.016; OR=1.2 per 10 unit increase; 95% CI: 1.0-1.4) and adiponectin (p=0.050; OR=1.5 per 10 unit increase; 95% CI: 1.0-2.4). Comparing SLE patients with and without plaque, there were no differences in cardiac CRP, complement, anti-dsDNA ab, CEC, sEPCR levels and EPCR SNP. However, sE-selectin and adiponectin levels were significantly higher in SLE with plaque compared to those without (sE-selectin 78 vs 52 ng/ml; p=0.006; adiponectin 18 vs 14 ug/ml; p=0.033). The estimated odds ratios for plaque in the final logistic regression model were: OR_selectin= 1.3 per 10 ng/ml increase (95% CI: 1.1-1.5) and OR_adiponectin=1.8 per 10 ug/ml increase (95% CI: 1.1-3.0). SELENA-SLEDAI scores were similar between groups, and the proportion of patients with SLEDAI<= 4 did not segregate with the absence of plaque. Neither past nor current medications significantly associated with plaque. In the stable subjects (SLEDAI <=4), age (p=0.007), sE-selectin (p=0.02) and adiponectin (p=0.02) remained associated with plaque. The prevalence of plaque was greatest in the stable patients with high sE-selectin plus high adiponectin (55%; p =0.0009) confirming the multivariable analyses. Sixty-two patients donated blood at a second visit. High sE-selectin and adiponectin were sustained in plaque patients compared to non-plaque patients (p=0.0009 and p=0.0011 respectively). Conclusion: These results confirm that SLE patients, irrespective of race, are at increased risk for premature atherosclerosis and support the hypothesis that endothelial perturbation is contributory even in the absence of clinically measurable disease activity

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

This study assessed the effect of transtricuspid placement of permanent pacemaker (PPM) and implantable cardioverter defibrillator (ICD) leads on tricuspid regurgitation (TR) in 248 patients with echocardiograms before and after placement. Some 21.2% of patients with baseline mild TR or less developed abnormal TR (3.4% mild-moderate, 12.8% moderate, 1.1% moderate-severe, 3.9% severe) after implant. TR worsened by 1 grade or more after implant in 24.2% (20.7% of PPMs vs. 32.4% of ICDs; P < .05). TR worsening was more common with ICDs than PPMs in patients with baseline mild TR or less. After lead implantation, abnormal TR developed in 21.2% and severe TR developed in 3.9% of patients with initially normal TR. TR worsened by at least 1 grade in 24.2%. Patients with ICDs had a higher rate of TR worsening compared with patients with PPMs (32.4% vs. 20.1%; P < .05)