Faculty Bibliography

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

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)

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

Aims Previous studies suggested haemodynamic benefits and, possibly, mortality reduction with the use of nitric oxide synthase (NOS) inhibition in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). We assessed preliminary efficacy and safety of four doses of l-n-monomethyl-arginine (l-NMMA), a non-selective NOS inhibitor, in patients with AMI complicated by CS despite an open infarct-related artery. Methods and results Patients (n = 79) were randomly assigned to a bolus and 5 h infusion of placebo or 0.15, 0.5, 1.0, or 1.5 mg/kg of l-NMMA. The primary outcome measure was absolute change in mean arterial pressure (MAP) at 2 h. Fifteen minutes after study drug initiation, mean change in MAP was -4.0 mmHg in the placebo group and 5.8 (P = 0.02), 4.8 (P = 0.02), 5.1 (P = 0.07), and 11.6 (P < 0.001) mmHg in the four l-NMMA groups, respectively (all vs. placebo). Mean change in MAP at 2 h was -0.4, 4.4, 1.8, -4.1, and 6.8 mmHg in the placebo and four l-NMMA groups, respectively (all P = NS). Conclusion l-NMMA resulted in modest increases in MAP at 15 min compared with placebo but there were no differences at 2 h