An overview of left atrial appendage occlusion devices.

Atrial fibrillation (AF) places patients at increased risk of thromboembolic events that can be devastating. The left atrial appendage (LAA) has been identified as the source of thrombus formation in nonvalvular AF. Traditionally, systemic anticoagulation has been used to reduce the risk of stroke and systemic embolism. However, anticoagulation is not well tolerated in all patients and is underutilized. As a potential alternative to anticoagulation, novel therapies have been developed to remove the LAA. Three main techniques are being utilized to accomplish LAA exclusion: percutaneous intracardiac, percutaneous epicardial, and surgical approaches. Emerging evidence suggests that LAA exclusion may be an effective means of reducing the risk of stroke in patients with nonvalvular AF.

Wnt5a, TLR2 and TLR4 are elevated in advanced human atherosclerotic lesions.

OBJECTIVE AND DESIGN: Atherosclerosis (ATH) is a chronic inflammatory disease that involves cascades of signaling events mediated by various effector proteins. Here we sought to determine if the expression of Wnt5a, a secreted glycoprotein, is altered in discrete regions of the arterial plaque. METHODS: Atherosclerotic plaque tissues from 14 human subjects undergoing elective carotid endarterectomy were used in this study. Immunohistochemistry and laser capture microdissection combined with quantitative real-time PCR were used to determine the expression of Wnt5a and Toll-like receptors (TLRs) in different sections of the arterial lesions. Atherosclerotic serum samples (n = 30) and serum from healthy subjects (n = 16) were quantified for Wnt5a using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The data analysis revealed that Wnt5a transcripts and protein were elevated in advanced arterial lesions relative to less advanced arterial lesions; that Wnt5a expression correlated with the presence of TLR4 and TLR2 transcripts; and that the average amount of Wnt5a protein present in atherosclerotic patient serum was significantly higher compared to healthy controls. CONCLUSIONS: This study is the first to provide evidence that the expression of Wnt5a increases as the disease progresses to a more advanced stage, and that this expression is coincident with that of TLR2 and TLR4. In addition, we found that the average Wnt5a levels in the serum of atherosclerotic patients are elevated relative to healthy controls, which is consistent with the hypothesis that Wnt5a plays a role in ATH.

Disparate Impact of Ischemic Injury on Regional Wall Dysfunction in Acute Anterior vs Inferior Myocardial Infarction.

BACKGROUND: Acute transmural ischemia should induce similar magnitude of wall motion abnormality (WMA) in both anterior myocardial infarction (AMI) and inferior (IMI). However, patients with AMI generally suffer more severe hemodynamic compromise. METHODS: This retrospective study compared WMA's in ST segment elevation MI patients undergoing primary reperfusion and subsequent cardiac MRI. Regional systolic wall motion and thickening were assessed in all segments throughout the left ventricle (LV). RESULTS: We analyzed 37 patients (AMI = 24 vs IMI = 13). Reperfusion success was achieved in all and there were no differences between groups in door-to-balloon time (AMI median 77 vs IMI 119 min, p = 0.085). Compared to IMI, in AMI LV ejection fraction was more depressed (37 ±â€¯7.6% vs 51 ±â€¯10.3%, P = 0.0006) and regional WMA more severe (total regional WMA score = 2.63 ±â€¯0.53 vs IMI = 2.1 ±â€¯0.52, P = 0.007). Regional dyskinesis was commonly observed in AMI patients but was rare in IMI (79% vs 7% of cases). Similarly, AMI manifested systolic thinning, whereas thickening was depressed but still present in IMI patients. Strikingly, WMA severity differed downstream relative to the origin of the infarct artery: In all AMI cases, WMA worsened from proximal anterior toward the distal apical zone; in IMI the pattern was reverse, with WMA consistently most severe in the basal segment of the inferior-posterior wall with preservation toward the apical distribution of the infarct vessel. CONCLUSION: These results demonstrate a disparate impact of ischemic injury on mechanical performance of the anterior vs inferior-posterior walls. These findings may be attributable to differences between the walls in architecture, mechanics and coronary blood flow. These observations may have implications for myocardial salvage, remodeling and prognosis.

The role of renal denervation in the treatment of hypertension.

OPINION STATEMENT: Resistant hypertension remains a difficult clinical disease to treat. It is known to place a patient at higher risk for developing significant cardiovascular, renal, and cerebrovascular disease. There is a current surge in research investigating renal denervation as potential treatment for resistant hypertension, as an overactive renal sympathetic system is known to exert an influence on the underlying pathophysiology. Several small studies have been published, with more underway, evaluating multiple different catheter-based systems that utilize radiofrequency ablation or ultrasound wave energy. These studies are showing promising results, with reduction in office blood pressure for the majority of patients. However, it appears that this does not always translate into definitive real-world observational effects. Variability exists in the number of patients that are able to reduce the amount of medication they take for hypertension, with some requiring an increase in medication. As a result, a more intensive screening process has been proposed, evaluating specific key predictors that may translate into a more favorable clinical response to renal denervation. We recommend that individuals with resistant hypertension continue to be optimized medically, adequately screened for secondary causes of hypertension, and that they consider participation in a renal denervation clinical trial to aid in further advancing the field.