Mitchell J. Silver

Cutting balloon angioplasty of the popliteal and infrapopliteal vessels for symptomatic limb ischemia

Options for lower limb percutaneous revascularization are limited especially for complex vessel obstruction. Cutting balloon angioplasty (CBA) has been described in the coronary literature as effective for complex disease. We analyzed our peripheral vascular database and report procedural outcomes along with the clinical success at a mean of 1‐year follow‐up in 73 patients with symptomatic lower limb ischemia undergoing CBA. CBA was successfully completed in all 73 patients (93 vessels; 100%) with predilation necessary in 4% of vessels. Severe intimal dissection or inadequate hemodynamic result necessitated in adjunctive stenting in 20%. There were no incidents of vessel perforation or surgical target vessel revascularization. One patient (1.5%) died during the periprocedural period due to renal failure. After mean follow‐up of 1 year (6–21 months), 89.5% of threatened limbs were salvaged. CBA is a safe and feasible option for the treatment of popliteal and infrapopliteal vessels. Catheter Cardiovasc Interv 2004;61:1–4.

Wnt5a is expressed in murine and human atherosclerotic lesions

Atherosclerosis is an inflammatory disease involving the accumulation of macrophages in the intima. Wnt5a is a noncanonical member of the Wnt family of secreted glycoproteins. Recently, human macrophages have been shown to express Wnt5a upon stimulation with bacterial pathogens in vitro and in granulomatous lesions in the lung of Mycobacterium tuberculosis-infected patients. Wnt5a expression has also been liked to Toll-like receptor-4 (TLR-4), an innate immune receptor implicated in atherosclerosis. These observations, along with the fact that Wnt5a is involved in cell migration and proliferation, led us to postulate that Wnt5a plays a role in atherosclerosis. To investigate this hypothesis, we characterized Wnt5a expression in murine and human atherosclerotic lesions. Tissue sections derived from the aortic sinus to the aortic arch of apolipoprotein E-deficient mice and sections derived from the carotid arteries of patients undergoing endarterectomy were subjected to immunohistochemical analysis. All samples were found to be positive for Wnt5a with predominant staining in the areas of macrophage accumulation within the intima. In parallel, we probed for the presence of TLR-4 and found coincident TLR-4 and Wnt5a expression. For both the Wnt5a and TLR-4 staining, consecutive tissue sections treated with an isotype- and species-matched Ig served as a negative control and exhibited little, if any, reactivity. Quantitative RT-PCR revealed that Wnt5a mRNA expression in RAW264.7 murine macrophages can be induced by stimulation with LPS, a known ligand for TLR-4. Combined, these findings demonstrate for the first time Wnt5a expression in human and murine atherosclerotic lesions and suggest that cross talk between TLR-4 and Wnt5a is operative in atherosclerosis.

Functional and clinical outcomes of nitinol stenting with and without abciximab for complex superficial femoral artery disease: a randomized trial.

Objective: To evaluate the effect of glycoprotein IIb/IIIa inhibition during nitinol stenting, of superficial femoral occlusive disease. Background: Stent implantation in the superficial femoral artery has been associated with suboptimal results while Glycoprotein IIb/IIIa inhibitors have shown improved procedural results during coronary intervention. We evaluated abciximab infusion during (Smart Stent®) implantation in superficial femoral obstructions. Methods: We conducted a randomized placebo controlled trial. The two primary end points include: (1) 9‐month restenosis defined as a decrease in ankle brachial index and in‐stent duplex ultrasound restenosis: (2) adverse events defined as death (30 days) or repeat revascularization within 9 months. Results: Twenty‐seven patients were randomized to abciximab and 24 patients to control (placebo). The primary end point of cumulative restenosis occurred in 15.4% of patients administered abciximab and in 12% administered placebo (P = 0.873). The primary restenosis endpoint in diabetics and total occlusions were similar at 14.3% and 15.4% respectively. The composite end point of 30‐day mortality and 9‐month revascularization occurred in 5.8% abciximab and 0% (P = 0.274) placebo with no 30‐day deaths. Graded treadmill time and Rutherford class were all significantly improved in both groups, but the abciximab group did not appear to demonstrate any identifiable effect. Conclusion: (Smart Stent) nitinol stenting of the superficial femoral artery was associated with favorable functional outcomes at 9 months. Adjunctive abciximab did not appear to demonstrate any identifiable effect.

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

AbstractObjective and designnAtherosclerosis (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.MethodsAtherosclerotic 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 (nxa0=xa030) and serum from healthy subjects (nxa0=xa016) were quantified for Wnt5a using an enzyme-linked immunosorbent assay (ELISA).ResultsThe 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.ConclusionsThis 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.

The DENALI Trial: An Interim Analysis of a Prospective, Multicenter Study of the Denali Retrievable Inferior Vena Cava Filter

PURPOSEnTo assess safety and effectiveness of a nitinol retrievable inferior vena cava (IVC) filter in patients who require caval interruption to protect against pulmonary embolism (PE).nnnMATERIALS AND METHODSnTwo hundred patients with temporary indications for an IVC filter were enrolled in this prospective, multicenter clinical study. Patients undergoing filter implantation were to be followed for 2 years or for 30 days after filter retrieval. At the time of the present interim report, all 200 patients had been enrolled in the study, and 160 had undergone a retrieval attempt or been followed to 6 months with their filter in place. Primary study endpoints included technical and clinical success of filter placement and retrieval. Patients were also evaluated for recurrent PE, new or worsening deep vein thrombosis, and filter migration, fracture, penetration, and tilt.nnnRESULTSnClinical success of placement was achieved in 94.5% of patients (172 of 182), with a one-sided lower limit of the 95% confidence interval of 90.1%. Technical success rate of filter placement was 99.5%. Technical success rate of retrieval was 97.3%; 108 filters were retrieved in 111 attempts. In two cases, the filter apex could not be engaged with a snare, and one device was engaged but could not be removed. Filter retrievals occurred at a mean indwell time of 165 days (range, 5-632 d). There were no instances of filter fracture, migration, or tilt greater than 15° at the time of retrieval or 6-month follow-up.nnnCONCLUSIONSnIn this interim report, the nitinol retrievable IVC filter provided protection against pulmonary embolism, and the device could be retrieved with a low rate of complications.

Increased Wnt5a mRNA Expression in Advanced Atherosclerotic Lesions, and Oxidized LDL Treated Human Monocyte-Derived Macrophages

Objective Wnt5a is a secreted glycoprotein highly present in atherosclerotic lesions. Uptake of oxidized-low density lipoprotein (ox-LDL) by monocytes/macrophages plays a critical role in atherosclerosis. The objective of this study was to determine if Wnt5a mRNA expression correlates with the severity of atherosclerotic lesions, and if, ox-LDL can induce Wnt5a mRNA in macrophages. Methods Wnt5a mRNA in tissue sections from carotid arteries of patients undergoing endarterectomy was quantified via RT-PCR and correlated with plaque severity. Human monocyte-derived macrophages and differentiated THP-1 cells, a human monocytic cell line, were treated with ox-LDL or native-LDL. Subsequently, Wnt5a transcripts were quantified by RT-PCR. Results Regions of the arteries with more severe plaques had detectable and significant levels of Wnt5a mRNA, while regions of the arteries containing less vulnerable plaques had low or non-detectable Wnt5a. Ox-LDL, but not native-LDL, induced Wnt5a mRNA in both human monocyte-derived macrophages and differentiated THP-1 cells. Conclusion Our results demonstrate that the expression of Wnt5a correlates with the severity of atherosclerotic lesions, and that ox-LDL induces Wnt5a mRNA expression in human macrophages. These findings are consistent with the hypothesis that Wnt5a plays a critical role in atherosclerosis progression and that a source of Wnt5a is ox-LDL stimulated macrophages.

Analysis of the Final DENALI Trial Data: A Prospective, Multicenter Study of the Denali Inferior Vena Cava Filter

PURPOSEnTo report the final 2-year data on the efficacy and safety of a nitinol retrievable inferior vena cava (IVC) filter for protection against pulmonary embolism (PE).nnnMATERIALS AND METHODSnThis was a prospective multicenter trial of 200 patients with temporary indications for caval filtration who underwent implantation of the Denali IVC filter. After filter placement, all patients were followed for 2 years after placement or 30 days after filter retrieval. The primary endpoints were technical success of filter implantation in the intended location and clinical success of filter placement and retrieval. Secondary endpoints were incidence of clinically symptomatic recurrent PE, new or propagating deep vein thrombosis (DVT), and filter-related complications including migration, fracture, penetration, and tilt.nnnRESULTSnFilter placement was technically successful in 199 patients (99.5%). Filters were clinically successful in 190 patients (95%). The rate of PE was 3% (n = 6), with 5 patients having a small subsegmental PE and 1 having a lobar PE. New or worsening DVT was noted in 26 patients (13%). Filter retrieval was attempted 125 times in 124 patients and was technically successful in 121 patients (97.6%). The mean filter dwell time at retrieval was 200.8 days (range, 5-736 d). There were no instances of filter fracture, migration, or tilt greater than 15° at the time of filter retrieval or during follow-up.nnnCONCLUSIONSnThe Denali IVC filter exhibited high success rates for filter placement and retrieval while maintaining a low complication rate in this clinical trial.

Percutaneous Endovascular Aortic Aneurysm Repair for Abdominal Aortic Aneurysm

Purpose of ReviewThis review discusses the benefits of a completely percutaneous approach to endovascular aortic aneurysm repair (EVAR), and provides an outline as to how this is performed by a multidisciplinary team of cardiologists and cardiovascular surgeons at a quaternary care community hospital.Recent FindingsPercutaneous endovascular aortic aneurysm repair (PEVAR) as compared to EVAR utilizing surgical femoral artery exposure is associated with a significant reduction in operation time, length of stay, access site complications, patient discomfort, and procedural cost. Furthermore, PEVAR may be the preferred approach in patients presenting with aneurysm rupture, as the avoidance of general anesthesia has been associated with improved 30-day mortality.SummaryAssuming no contraindication based on vascular anatomy, clinical status, or patient preference, these findings suggest that in properly selected patients, PEVAR should be the primary method for abdominal aortic aneurysm repair in both stable and unstable patients.

The Role of Renal Denervation in the Treatment of Hypertension

Opinion statementResistant 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.