Prediction of coronary artery disease severity in patients referred for coronary angiography

BACKGROUND: Diagnostic coronary angiography is often followed by coronary stenting. Therapy with aspirin and clopidogrel is currently the standard treatment for patients undergoing coronary stenting. Clopidogrel loading is usually given prior to the procedure. Some pretreated patients, however, are found to have triple-vessel disease (3VD) or left main disease (LMD) that requires referral for coronary artery bypass graft (CABG) surgery. Surgery in patients pretreated with clopidogrel may be complicated by excessive bleeding or delayed to avoid that risk. HYPOTHESIS: A risk factor-based formula may predict the likelihood that patients referred for coronary angiography will have 3VD or LMD. METHODS: Consecutive patients (n = 2,180) referred for coronary angiography constitute the training subset (n = 1,296) used to build the model, and the validation subset (n = 884) used to test the model. Logistic regression models selected five variables showing strong associations with the presence of 3VD or LMD: age, gender, diabetes, hypercholesterolemia, and prior myocardial infarction (MI). A formula based on these variables and on the training subset was constructed to calculate the probability of 3VD or LMD. RESULTS: Applying this model to the validation subset predicted 3VD or LMD with 79% sensitivity, 53% specificity, 45% positive predictive value, and 83% negative predictive value. CONCLUSIONS: This simple formula based on five clinical variables is helpful in predicting the likelihood that patients, referred for coronary angiography, will have 3VD or LMD. Use of this formula can help decide in which patients clopidogrel loading prior to angiography should be avoided.     

Validity of the EQ-5D-5L and EQ-5D-3L in patients with Crohn’s disease

Quality of Life Research - The EuroQol five-dimension questionnaire (EQ-5D) is the most commonly used instrument to obtain utility values for cost-effectiveness analyses of treatments for...     

Formulation and delivery mode affect disposition and activity of tyrphostin-loaded nanoparticles in the rat carotid model

Poor drug residence in the arterial wall hinders clinical implementation of local drug delivery strategies for the treatment of restenosis. A rat carotid model of vascular injury and intraluminal delivery of tyrphostin-containing polylactic acid (PLA) nanoparticles (NPs) were used to determine the relationship between residence properties and biological activity of different formulations and administration modes. The effects of delivery modes (denudation and delivery time) and formulation variables (adsorbed vs encapsulated drug, and NP size) on arterial drug/NP retention were examined. Antirestenotic effects of large (160 nm) and small (90 nm) tyrphostin-containing NPs, surface-absorbed tyrphostin, and systemic treatment were compared. Fluorescent NPs were used to study the spatial distribution of the carrier in the arterial wall. The decrease in arterial tyrphostin level over time fitted a biexponential model. Delivery time and pressure, endothelium integrity, particle size, and drug-polymer association affected local pharmacokinetics and the antirestenotic results after 14 days. The PLA-based tyrphostin NP formulation ensured a prolonged drug residence at the angioplasty site after single intraluminal application. Several readily adjustable formulation and procedural factors considerably modified arterial ingress of the drug-loaded NPs and governed their subsequent redistribution, tissue binding, elimination, and ensuing antirestenotic effect.     

Treatment of post-catheterization femoral artery pseudo-aneurysm with para-aneurysmal saline injection

Femoral artery pseudoaneurysm is a common complication associated with cardiac catheterization procedures. Ultrasound-based techniques (e.g., mechanical compression, thrombin injection) and open surgical intervention are frequently used in the management of pseudoaneurysm. The investigators report their prospective experience with a novel method for the treatment of pseudoaneurysm after cardiac catheterization using ultrasound-guided, para-aneurysmal injection of physiologic saline. Sixty-four consecutive patients with pseudoaneurysms after cardiac catheterization were treated using normal saline (0.9% sodium chloride 25 to 60 ml) injected into the tissue surrounding the tract connecting the pseudoaneurysm with the femoral artery, followed by manual pressure of short duration. In none of the patients was concomitant antithrombotic therapy (aspirin [n = 63], clopidogrel [n = 45], unfractionated or low-molecular-weight heparin [n = 23], and warfarin [n = 5]) discontinued during the closure attempt. Fifty-nine of the 64 pseudoaneurysms (92%) were successfully occluded using saline injection. In 5 patients in whom saline injection failed, the pseudoaneurysms were successfully treated with thrombin injection (n = 4) or ultrasound-guided compression (n = 1). In all 64 patients, pseudoaneurysm closure was confirmed by ultrasound at 24 hours. The procedure was very well tolerated by the patients, and no side effects or complications were noted. In conclusion, ultrasound-guided saline injection affords a simple, safe, and effective alternative treatment for the closure of postcatheterization pseudoaneurysms.     

Coronary sinus reducer stent for the treatment of chronic refractory angina pectoris: a prospective, open-label, multicenter, safety feasibility first-in-man study.

OBJECTIVES: This study sought to evaluate the safety of the Coronary Sinus Reducer (Neovasc Medical, Inc., Or Yehuda, Israel) as a potential alternate therapy for patients with refractory angina who are not candidates for conventional revascularization procedures. BACKGROUND: Increased coronary sinus (CS) pressure can reduce myocardial ischemia by redistribution of blood from nonischemic to ischemic territories. The Coronary Sinus Reducer is a percutaneous implantable device designed to establish CS narrowing and to elevate CS pressure. In preclinical experiments, implantation of the Reducer was safe and was associated with improved ischemic parameters. In the present study, the safety and feasibility of the Coronary Sinus Reducer was evaluated in patients with refractory angina who were not candidates for revascularization. METHODS: Fifteen coronary artery disease patients with severe angina and reversible ischemia were electively treated with the Reducer. Clinical evaluation, dobutamine echocardiography, thallium single-photon emission computed tomography, and administration of an angina questionnaire were performed before and 6 months after implantation. Cardiac computed tomography was performed 2 days and 6 months after implantation. RESULTS: All procedures were completed successfully. No procedure-related adverse events occurred during the periprocedural and the follow-up periods. Angina score improved in 12 of 14 patients. Average Canadian Cardiovascular Society score was 3.07 at baseline and 1.64 at follow-up (n = 14, p < 0.0001). Stress-induced ST-segment depression was reduced in 6 of 9 patients and was eliminated in 2 of these 6 (p = 0.047). The extent and severity of myocardial ischemia by dobutamine echocardiography and by thallium single-photon emission computed tomography was reduced (p = 0.004 [n = 13] and p = 0.042 [n = 10], respectively). CONCLUSIONS: Implantation of the Coronary Sinus Reducer is feasible and safe. These findings, along with the clinical improvement observed, support further evaluation of the Reducer as an alternative treatment for patients with chronic refractory angina who are not candidates for coronary revascularization.     

Local delivery of platelet-derived growth factor receptor-specific tyrphostin inhibits neointimal formation in rats

Signal transduction through the platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR) system is involved in the process of postangioplasty restenosis. Tyrphostins are low molecular weight inhibitors of protein tyrosine kinases. We assessed the antiproliferative effects of PDGFRbeta-specific tyrphostin AG-1295 in vitro and in vivo. AG-1295 significantly inhibited rat smooth muscle cell growth stimulated by PDGF-BB or FCS. This antiproliferative effect was paralleled by reversible reduction of the total phosphotyrosine level and the degree of PDGFRbeta phosphorylation by the drug in vitro. Local sustained delivery of the drug from perivascularly implanted polymeric matrices resulted in focal AG-1295 levels of 711 and 29.1 ng/mg of dry arterial tissue 1 and 14 days after implantation in rats. AG-1295 delivered from polymeric matrices resulted in a 35% reduction of neointimal formation on day 14 after balloon injury in the rat carotid model. Tyrosine phosphorylation of certain transduction proteins in arterial tissue extracts was significantly upregulated by balloon injury on day 3 but was essentially returned to or below basal levels 14 days after injury. Tyrphostin treatment decreased tyrosine phosphorylation at both time points below the basal levels. Moreover, the enhancement of PDGFRbeta expression 3 and 14 days after arterial injury was strongly inhibited by AG-1295 treatment. It can be concluded that AG-1295 reduces neointimal formation by inhibiting PDGFbeta-triggered tyrosine phosphorylation.     

Exposure of hospital personnel to Brucella melitensis and occurrence of laboratory-acquired disease in an endemic area

In 1997, 7 cases of laboratory-acquired Brucella melitensis infections were detected among the hospital personnel of a medical centre serving an endemic area in southern Israel. Although the onset of symptoms in 6 of the 7 patients occurred during a 2-week period, suggesting a point source exposure, biotype analysis showed that the outbreak was caused by 3 different B. melitensis serovars, indicating multiple exposures. Review of the laboratory records showed that during 1997, the microorganism was recovered from 146 blood and synovial fluid cultures, and that during the 2 months in which the laboratory-acquired cases occurred (April and June), 53 of 530 positive aerobic blood culture bottles (10.0%) grew B. melitensis. The epidemiological investigation did not reveal the source of the outbreak, and no noticeable breaches in laboratory safety practices could be demonstrated. It is concluded that in areas endemic for brucellosis, hospital personnel are frequently exposed to Brucella microorganisms. Under these circumstances, significant morbidity may occur despite observance of recommended safety practices. Biotyping of Brucella isolates may contribute to the elucidation of complex epidemiological situations.