Current status of percutaneous PFO closure.

The clinical significance of persistent patent foramen ovale (PFO) is not well defined. Empirically, PFO has been associated with many clinical conditions. In cryptogenic stroke, migraine, and orthodeoxia/platypnea, a plausible biologic mechanism exists to support PFO closure as a possible treatment. Although transcatheter closure of PFO has been available for over 2 decades, it has remained controversial due to a paucity of evidence to guide patient and device selection. Contemporary studies investigating PFO closure as treatment for patients with these conditions have been published recently and longitudinal data regarding the safety and efficacy of the devices is now available. In this review, we aim to describe the potential clinical significance of a patent foramen in the adult, appraise the newest additions to the body of evidence, and discuss the safety, benefit, patient selection, and future of transcatheter treatment of PFO.

The evidence for treating hypertension in older people with dementia: a systematic review.

Hypertension and dementia commonly co-exist in older people, yet guidance is lacking on how to manage these co-existing conditions. The aim of this systematic review was to assess the evidence for the treatment of hypertension in older people with dementia. Medline, EMBASE, Cochrane Library and the national research register archives were searched. Inclusion criteria were: randomised controlled trial of hypertension treatment, included participants aged 65+ years, participants had a diagnosis of dementia (global cognitive decline for at least 6 months affecting daily function), and the study assessed cognitive outcomes using validated tools. Dementia prevention studies and poor quality studies were excluded. The initial search revealed 1178 papers of potential interest, of which 24 were selected for review and six met the full inclusion criteria. Trials included people with mild-to-moderate but not severe dementia; exclusion criteria for the trials were extensive. Four trials were placebo-controlled RCTs; the remaining two compared different antihypertensives. All trials reported MMSE scores at baseline and follow-up; four reported blood pressure changes at follow-up; and only three reported cardiovascular morbidity or mortality at follow-up. Only one of four placebo-controlled studies showed evidence of blood pressure reduction, but no clear evidence for benefit (or harm) from antihypertensives on cognition, physical function or other cardiovascular outcomes. We found no evidence to confirm or refute the hypothesis that treatment of hypertension in people with dementia leads to overall health benefit.

The ABCD and ABCD2 as predictors of stroke in transient ischemic attack clinic outpatients: a retrospective cohort study over 14 years.

BACKGROUND: The ABCD and ABCD2 scores have been validated for use as predictors of stroke in community populations up to 90 days after a transient ischemic attack (TIA). TIA outpatient clinics may see a selective group of patients who have not had an early stroke but may be at raised risk in the medium to long term and therefore benefit from preventive treatment. AIM: To describe the prognostic values of the ABCD and ABCD2 scores on long-term stroke risk. DESIGN: Retrospective cohort study of TIA clinic outpatients followed for up to 14 years. METHODS: Absolute and relative stroke risks, Kaplan-Meier survival curves and cumulative stroke incidence were calculated. Receiver Operating Characteristic curves (ROCs) and areas under the curve were calculated for both scores. RESULTS: Seven hundred and ninety-five patients were included and 138 (17.3%) experienced a stroke within 13.8 years follow-up after first TIA clinic visit, a crude risk of 26.3 per 1000 person-years. Compared with baseline scores of 0-2, risk ratios for ABCD of 3-4 were 2.95 (95% CI 1.52-6.40), and for 5-6 were 3.42 (95% CI 1.72-7.54); for the ABCD2, risk ratios for 3-4 were 2.68 (95% CI 1.37-5.84), and for 5-7 were 3.55 (95% CI 1.80-7.79). Scores of > or = 3 for either ABCD or ABCD2 predicted raised stroke risks at 90 days, 1, 5 and 10 years. Areas under the curve were 0.619 (95% CI 0.571-0.668) and 0.630 (95% CI 0.582-0.677) for the ABCD and ABCD2 scores, respectively. CONCLUSION: ABCD and ABCD2 scores of > or = 3 may be clinically useful in identifying TIA outpatients at raised risk of stroke in the medium to long term.

Comparison of results of percutaneous balloon mitral commissurotomy in patients aged > or = 65 years with those in patients aged < 65 years.

Percutaneous balloon mitral commissurotomy (PBMC) is now first-line therapy in patients with symptomatic mitral stenosis (MS) and favorable valve morphology. Unfortunately, the outcome of Medicare-aged patients undergoing this procedure has not previously been defined. The results of PBMC in 55 patients > or = 65 years old (71 +/- 6 years) with moderate or severe MS were compared with 268 younger patients (47 +/- 10). Preprocedural New York Heart Association functional class and pulmonary pressures did not differ. The older patients had higher blood pressure, were more likely to be in atrial fibrillation and had higher valve scores (9.9 +/- 2.5 vs 8.6 +/- 2.2, p = 0.001). Procedural success was higher in the younger group (71% vs 55%, p = 0.013), with a greater increase in mitral valve area. Complications were similar in both groups and there were no periprocedural deaths. At 6 months a significant improvement in function class was seen in both groups. Restenosis, as assessed by serial echocardiography, occurred at a rate of 0.06 cm(2)/year in both groups, and functional class remained unchanged over 3 years. Event-free survival was similar at 48 months: 76% in the younger group and 69% in the older group. Our data thus demonstrates that PBMC can be safely performed in the Medicare-aged population. Despite less acute success in the older population, complication rates do not differ and decrement in valve area over time occurs at a similar rate. Functional class remains improved and event-free survival over 4 years appears similar in both groups. PBMC should thus be offered to patients with MS and suitable anatomy regardless of their age.

Congenital unilateral pulmonary vein atresia: radiologic findings in three adult patients.

OBJECTIVE: The purpose of our study is to describe the radiologic findings of adult patients presenting with congenital unilateral pulmonary vein atresia. CONCLUSION: Chest radiography in affected patients typically reveals a small hemithorax and ipsilateral pulmonary artery as well as ipsilateral septal thickening. CT shows, in addition, ground-glass attenuation, the absence of a pulmonary vein connection to the left atrium, and abundant mediastinal venous collateral vessels. MR imaging is helpful in further characterizing the vascular abnormalities. Angiography may help to confirm the diagnosis.

Correlation between quantitative left atrial spontaneous echocardiographic contrast and intact fibrinogen levels in mitral stenosis.

An association between left atrial spontaneous echocardiographic contrast (LASEC) and thromboembolic events has been recognized. However, the appearance of LASEC and the assessment of its intensity are gain dependent. To evaluate the relation between LASEC intensity and coagulation activity, 11 patients with mitral stenosis underwent transesophageal echocardiography with quantitative integrated backscatter assessment of LASEC. Right and left atrial blood samples were evaluated for concentrations of coagulation markers, including intact fibrinogen, fibrinopeptide A, D-dimer, prothrombin fragment 1+2, and thrombin-antithrombin III complex. The patients were found to have significantly higher mean left atrial concentrations compared with right atrial concentrations of thrombin-antithrombin III (28.46 +/- 21.05 versus 3.21 +/- 7.16 ng/mL, respectively; P =.001) and fibrinopeptide A (32.78 +/- 17.54 versus 7.42 +/- 8.27 nmol/L, respectively; P <.001). Intact fibrinogen levels were similar in both atria, and a strong, direct correlation existed between left and right atrial intact fibrinogen levels (r = 0.78, P =.005). Quantitative integrated backscatter of LASEC correlated directly with left atrial fibrinogen level (r = 0.78, P =.013) but not with markers of thrombin generation (thrombin-antithrombin III) or activity (fibrinopeptide A). Our results confirm that patients with mitral stenosis have evidence of a regional hypercoagulable state in the left atrium. However, the intensity of LASEC assessed by quantitative integrated backscatter correlates with both right and left atrial intact fibrinogen level, a systemic marker of coagulation.

Mutational analysis of the fractalkine chemokine domain. Basic amino acid residues differentially contribute to CX3CR1 binding, signaling, and cell adhesion.

Fractalkine (FKN/CX3CL1) is a unique member of the chemokine gene family and contains a chemokine domain (CD), a mucin-like stalk, a single transmembrane region, and a short intracellular C terminus. This structural distinction affords FKN the property of mediating capture and firm adhesion of FKN receptor (CX3CR1)-expressing cells under physiological flow conditions. Shed forms of FKN also exist, and these promote chemotaxis of CX3CR1-expressing leukocytes. The goal of the present study was to identify specific residues within the FKN-CD critical for FKN-CX3CR1 interactions. Two residues were identified in the FKN-CD, namely Lys-7 and Arg-47, that are important determinants in mediating an FKN-CX3CR1 interaction. FKN-K7A and FKN-R47A mutants exhibited 30-60-fold decreases in affinity for CX3CR1 and failed to arrest efficiently CX3CR1-expressing cells under physiological flow conditions. However, these mutants had differential effects on chemotaxis of CX3CR1-expressing cells. The FKN-K7A mutant acted as an equipotent partial agonist, whereas the FKN-R47A mutant had marked decreased potency and efficacy in measures of chemotactic activity. These data identify specific structural features of the FKN-CD that are important in interactions with CX3CR1 including steady state binding, signaling, and firm adhesion of CX3CR1-expressing cells.

Aortic dissection after angioplasty and stenting of an aortic coarctation: detection by intravascular ultrasonography but not transesophageal echocardiography.

In this case report, an iatrogenic dissection of the descending aorta occurred during balloon angioplasty and stenting of a recurrent coarctation. The dissection was not seen by transesophageal echocardiography, but intravascular ultrasonography, performed routinely during such procedures at this institution, identified the dissection and guided further therapeutic stent placement.

Chemokines and Alzheimer's disease.

In recent years, increasing attention has been focused on chemokines as inflammatory mediators in the CNS. The limited number of studies that have investigated chemokine and chemokine receptor expression in Alzheimer's disease (AD) brain and in cell culture models seem to support a role for inflammation in AD pathogenesis. Here we provide a review of these studies, but in addition, point out the possible role of chemokines as communication molecules between neurons and microglia. Understanding neuron-microglia interactions is essential for understanding AD pathogenesis, and disturbances in chemokine-mediated intercellular communication may contribute toward a generalized impairment of microglial cell function.

Inhaled nitric oxide selectively dilates pulmonary vasculature in adult patients with pulmonary hypertension, irrespective of etiology.

OBJECTIVES: We sought to compare the responses of patients with pulmonary hypertension from primary and secondary causes (PPH and SPH, respectively) to inhaled nitric oxide (iNO) in the cardiac catheterization laboratory. BACKGROUND: Pulmonary hypertension can lead to right ventricular pressure overload and failure. Although vasodilators are effective as therapy in patients with PPH, less is known about their role in adults with SPH. Inhaled nitric oxide can accurately predict the response to other vasodilators in PPH and could be similarly utilized in SPH. METHODS: Forty-two patients (26 to 77 years old) with pulmonary hypertension during cardiac catheterization received iNO. Demographic and hemodynamic data were collected. Their response to iNO was defined by a decrease of > or =20% in mean pulmonary artery (PA) pressure or pulmonary vascular resistance (PVR). RESULTS: Mean PA pressures and PVR were lower during nitric oxide (NO) inhalation in all patients with pulmonary hypertension. Seventy-eight percent of patients with PPH and 83% of patients with SPH were responders to iNO. A trend was seen toward a greater response with larger doses of NO in patients with SPH. Nitric oxide was a more sensitive predictor of response (79%), compared with inhaled oxygen (64%), and was well tolerated, with no evidence of systemic effects. Elevation in right ventricular end-diastolic pressure appeared to predict poor vasodilatory response to iNO. CONCLUSIONS: Nitric oxide is a safe and effective screening agent for pulmonary vasoreactivity. Regardless of etiology of pulmonary hypertension, pulmonary vasoreactivity is frequently demonstrated with the use of NO. Right ventricular diastolic dysfunction may predict a poor vasodilator response.

Congenital agenesis of the right pulmonary artery.

A 44-year-old woman with recurrent pulmonary infections developed severe hemoptysis. Chest radiography revealed a hypoplastic right lung. Absence of the right pulmonary artery, a very rare congenital anomaly, was demonstrated by computed tomography and cardiac catheterization. Severe pulmonary hypertension in the contralateral lung precluded right pneumonectomy but percutaneous embolization of a large systemic arterial collateral to the right lung provided palliative relief of hemoptysis.

Contrast Agents for Cardiac Angiography: Osmolality and Contrast Complications.

Radiographic contrast agents have undergone a tremendous evolution over the past several decades. The creation of contrast agents with greater iodine carrying capacity and lower osmolality has improved imaging quality and reduced complications, including nausea, vomiting, congestive heart failure, and cardiac rhythm abnormalities. Whether differences exist among agents in terms of thrombotic complications remains controversial. Several characteristics including potential complications, toxicity, and cost must factor into the decision to use a particular contrast agent in cardiac procedures.

Acute excitotoxic injury induces expression of monocyte chemoattractant protein-1 and its receptor, CCR2, in neonatal rat brain.

Chemokines are a family of structurally related cytokines that activate and recruit leukocytes into areas of inflammation. The "CC" chemokine, monocyte chemoattractant protein (MCP)-1 may regulate the microglia/monocyte response to acute brain injury. Recent studies have documented increased expression of MCP-1 in diverse acute and chronic experimental brain injury models; in contrast, there is little information regarding expression of the MCP-1 receptor, CCR2, in the brain. In the neonatal rat brain, acute excitotoxic injury elicits a rapid and intense microglial response. To determine if MCP-1 could be a regulator of this response, we evaluated the impact of excitotoxic injury on MCP-1 and CCR2 expression in the neonatal rat brain. We used a reproducible model of focal excitotoxic brain injury elicited by intrahippocampal injection of NMDA (10 nmol) in 7-day-old rats, to examine injury-induced alterations in MCP-1 and CCR2 expression. RT-PCR assays demonstrated rapid stimulation of both MCP-1 and CCR2 mRNA expression. MCP-1 protein content, measured by ELISA in tissue extracts, increased >30-fold in lesioned tissue 8-12 h after lesioning. CCR2 protein was also detectable in tissue extracts. Double-immunofluorescent labeling enabled localization of CCR2 both to activated microglia/monocytes in the corpus callosum adjacent to the lesioned hippocampus and subsequently in microglia/monocytes infiltrating the pyramidal cell layer of the lesioned hippocampus. These results demonstrate that in the neonatal brain, acute excitotoxic injury stimulates expression of both MCP-1 and its receptor, CCR2, and suggests that MCP-1 regulates the microglial/monocyte response to acute brain injury.

Randomized trial of contrast media utilization in high-risk PTCA: the COURT trial.

BACKGROUND: Previous in vitro and in vivo studies have suggested an association between thrombus-related events and type of contrast media. Low osmolar contrast agents appear to improve the safety of diagnostic and coronary artery interventional procedures. However, no data are available on PTCA outcomes with an isosmolar contrast agent. METHODS AND RESULTS: A multicenter prospective randomized double-blind trial was performed in 856 high-risk patients undergoing coronary artery intervention. The objective was to compare the isosmolar nonionic dimer iodixanol (n=405) with the low osmolar ionic agent ioxaglate (n=410). A composite variable of in-hospital major adverse clinical events (MACE) was the primary end point. A secondary objective was to evaluate major angiographic and procedural events during and after PTCA. The composite in-hospital primary end point was less frequent in those receiving iodixanol compared with those receiving ioxaglate (5.4% versus 9.5%, respectively; P=0.027). Core laboratory defined angiographic success was more frequent in patients receiving iodixanol (92.2% versus 85. 9% for ioxaglate, P=0.004). There was a trend toward lower total clinical events at 30 days in patients randomized to iodixanol (9.1% versus 13.2% for ioxaglate, P=0.07). Multivariate predictors of in-hospital MACE were use of ioxaglate (P=0.01) and treatment of a de novo lesion (P=0.03). CONCLUSIONS: In this contemporary prospective multicenter trial of PTCA in the setting of acute coronary syndromes, there was a low incidence of in-hospital clinical events for both treatment groups. The cohort receiving the nonionic dimer iodixanol experienced a 45% reduction in in-hospital MACE when compared with the cohort receiving ioxaglate.

NF-kappaB-dependent fractalkine induction in rat aortic endothelial cells stimulated by IL-1beta, TNF-alpha, and LPS.

Fractalkine is an endothelial cell-derived CX3C chemokine that is chemotactic mainly to mononuclear cells. Fractalkine was induced in rat aortic endothelial cells (RAEC) by interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and lipopolysaccharide (LPS) transcriptionally and translationally. This induction correlated with increased NF-kappaB DNA binding activity as determined by gel mobility shift assay. Supershift assays revealed that the NF-kappaB subunits p50 and p65 were responsible for kappaB binding. Accordingly, we examined the role of NF-kappaB in fractalkine induction in RAEC through the use of an adenovirus-mediated mutant IkappaB as a specific inhibitor. Delivery of a dominant-negative form of IkappaBalpha in RAEC dramatically reduced the induction of fractalkine by these stimuli, suggesting a role for NF-kappaB activation in fractalkine induction. The inhibition of fractalkine expression by two potent NF-kappaB inhibitors, sulfasalazine and sanguinarine, further supported the central role of NF-kappaB in fractalkine transcription regulation and suggested a novel therapeutic target aimed at modulating leukocyte endothelial cell interaction.

Percutaneous stenting of right pulmonary artery stenosis in fibrosing mediastinitis.

Pulmonary artery stenosis is an uncommon complication of fibrosing mediastinitis. Previous medical and surgical therapies have provided limited clinical efficacy without objective evidence of clinical improvement. With the advantages of limited invasiveness and absent need for prolonged drug therapy, percutaneous stent deployment to relieve pulmonary artery obstruction represents a novel treatment for this rare disorder.