Safety and efficacy of local periadventitial delivery of sirolimus for improving hemodialysis graft patency: first human experience with a sirolimus-eluting collagen membrane (Coll-R).

BACKGROUND: Neointimal hyperplasia causes a high rate of hemodialysis synthetic graft failure. Thus, therapies that inhibit neointimal hyperplasia are urgently needed. The Coll-R is a sirolimus-eluting collagen matrix designed for intra-operative perivascular implantation around the graft-venous anastomosis. Sirolimus is an anti-proliferative drug that has proven clinical utility in suppressing neointimal tissue growth in coronary artery disease when delivered locally to the vascular wall by an endovascular drug eluting stent. METHODS: A cohort of 12 chronic hemodialysis patients underwent surgical placement of 13 polytetrafluoroethylene grafts + Coll-R and were followed for up to 24 months. The primary endpoint was safety (freedom from device related adverse events). Secondary endpoints were pharmacokinetics of sirolimus release, success of Coll-R implantation and primary unassisted graft patency. RESULTS: There were no technical failures, infections, vascular anastomotic or wound-healing problems. Whole blood sirolimus levels rose to a mean peak of 4.8 ng/mL at 6 h and fell to <1 ng/mL at 1 week (n = 5). Twelve and 24-month primary unassisted patencies were 76 and 38%, respectively, and the thrombosis rate was 0.37/patient-year. CONCLUSIONS: Perivascular implantation of the Coll-R during graft surgery safely delivered sirolimus to the vascular wall. Systemic sirolimus levels were sub-therapeutic for immunosuppression. This small first-in-human study supports the concept that the Coll-R can safely deliver sirolimus to the graft-venous anastomosis. Safety and patency in this small study were sufficiently encouraging to justify randomized controlled trials to further test the efficacy of the Coll-R.

One-year clinical outcomes, midterm survival, and predictors of mortality after carotid stenting in elderly patients.

BACKGROUND: It has been demonstrated recently that carotid stenting can be performed safely in patients > or =80 years of age. However, it is uncertain whether these patients will derive benefit because longevity after revascularization is an important consideration. This study was conducted to determine survival and predictors of mortality of selected elderly patients after stenting. METHODS AND RESULTS: One hundred forty-two consecutive elderly patients who were non-high risk for stenting underwent 153 procedures. Patients had either symptomatic stenosis > or =50% or asymptomatic stenosis > or =70%. Demographics and in-hospital outcomes were entered into a database; subsequent outcomes and mortality data were obtained retrospectively. Mean+/-SD age was 83.3+/-3.1 years. Symptomatic patients accounted for 28%. Overall survival at 3 years was 76% (85% at 2 years). At 1 year, 1 fatal stroke had occurred, with 97% of survivors (n=114) free of neurological events (neurological status was undetermined in the remaining 3%). Predictors of mortality were remote (> or =6 months) transient ischemic attack or cerebrovascular accident, smoking history, and creatinine clearance (hemoglobin level showed a strong trend toward achieving significance); for the asymptomatic subgroup, predictors of mortality were smoking history, previous carotid endarterectomy, hemoglobin level, and increasing age. In particular, symptom status and sex were not independent predictors of mortality. CONCLUSIONS: This study demonstrates that in selected elderly patients, a high proportion (85%) survived 2 years and >75% survived 3 years after stenting. Carotid stenting may be considered a revascularization option in such patients. Better selection of patients using the predictors of mortality may help to reduce unwarranted procedures and to optimize survival likelihood.

Carotid stenting and bivalirudin with and without vascular closure: 3-year analysis of procedural outcomes.

OBJECTIVES: The purpose of this study was to examine the outcome of carotid stenting using bivalirudin and the influence of vascular closure devices (VCD) on the incidence and severity of peri-procedural hypotension. BACKGROUND: Bivalirudin, a short-acting direct thrombin inhibitor, has been shown to be an effective anticoagulant in coronary interventions, with less risk of bleeding compared with heparin. Routine use of VCD has become the standard of care, facilitating patient ambulation after percutaneous carotid and coronary interventions. The combined use of these two therapies (bivalirudin and VCD) may improve outcomes in carotid interventions where prolonged patient immobilization may exacerbate hypotension following stenting. METHODS: A total of 514 patients underwent 536 carotid stenting procedures in the 3-year period from September 2004 to September 2007. All patients received adjunctive bivalirudin, with and without VCD. This cohort was analyzed for peri-procedural and 30-day clinical outcomes and length of hospitalization. RESULTS: Thirty-day stroke and death rate was 1.7%. A total of 83 patients (15.4%) experienced intra- or post-procedural hypotension (systolic BP < 80 mm Hg). There were four (0.7%) major bleeding complications requiring transfusion, and length of stay was delayed more than 24 hr in five patients (0.93%), all of whom were in the manual compression group. CONCLUSIONS: This was a negative study, with no significant difference on prolonged hypotensive events in patients with vascular closure device and bivalirudin, compared with those with manual compression and bivalirudin. Vascular closure devices were safe and effective with a low incidence of complications. In carotid artery stenting, bivalirudin is safe with low incidence of major bleeding and acceptable 30-day adverse event rates (stroke and death).

COVID-19 follow-up planning: what will we be missing?

There is a real need for a discharge plan for COVID-19 survivors in the UK. Follow-up imaging could help assess the resolution of infection, exclude underlying malignancy and identify post-inflammatory fibrosis. https://bit.ly/2YJ8hyg.

Carotid artery stenting in elderly patients: importance of case selection.

OBJECTIVES: This study was conducted to determine if carotid stenting (CS) could be safely performed in the elderly. BACKGROUND: Age has been shown to be a predictor of neurological complications during CS. We postulated that CS could be safely performed in elderly patients if certain anatomical and clinical markers such as excessive vascular tortuosity, heavy concentric calcification of the lesion, and decreased cerebral reserve were avoided. METHODS: From July 2003 to October 2007, 142 patients aged > or =50% or asymptomatic stenosis > or =70%. All patients underwent carotid and cerebral angiography to determine anatomic suitability and stent risk. Demographic and outcome data were entered into a database; other data were obtained retrospectively. Independent neurology evaluation was performed before and at 24 hr after the procedure. RESULTS: The mean age was 83.2 years, 62% were male, 25.5% were symptomatic, 8.5% had postcarotid endarterectomy restenosis, and 6.0% had contralateral internal carotid artery occlusion. There were no intracranial hemorrhages or periprocedural myocardial infarctions. One patient had amaurosis fugax. There were two minor and three major strokes in-hospital (3.3%). All patients had 30-day follow-up. One of the major strokes expired. Thus the overall 30-day stroke or death rate was 3.3% and major stroke or death rate was 2.0%. The 30-day stroke or death rate was 5.1% for symptomatic patients and 2.6% for asymptomatic patients. CONCLUSION: CS can be performed safely in anatomically suitable elderly patients with low adverse event rates. CS should remain a revascularization option in appropriately selected elderly patients.

Realizing the potential of carotid artery stenting: proposed paradigms for patient selection and procedural technique.

Carotid artery stenting, compared with carotid endarterectomy, is emerging as an effective and less invasive method of revascularization for extracranial carotid artery stenosis. Carotid stenting is established as the treatment of choice for certain high-risk patient subsets, and ongoing clinical trials are evaluating this method across a broader clinical spectrum, including asymptomatic patients. For carotid stenting to reach its full potential, an acceptable risk of periprocedural complications, particularly in low-risk patients, must be ensured (the "3% rule"). The present article provides an in-depth review of carotid stenting, with special emphasis on the process of risk stratification pertaining to clinical, anatomic, and procedural considerations necessary to optimize procedural safety and patient outcomes.

Bifurcation coronary lesions treated with the "crush" technique: an intravascular ultrasound analysis.

OBJECTIVES: We report intravascular ultrasound (IVUS) findings after crush-stenting of bifurcation lesions. BACKGROUND: Preliminary results with the crush-stent technique are encouraging; however, isolated reports suggest that restenosis at the side branch (SB) ostium continues to be a problem. METHODS: Forty patients with bifurcation lesions underwent crush-stenting with the sirolimus-eluting stent. Postintervention IVUS was performed in both branches in 25 lesions and only the main vessel (MV) in 15 lesions; IVUS analysis included five distinct locations: MV proximal stent, crush area, distal stent, SB ostium, and SB distal stent. RESULTS: Overall, the MV minimum stent area was larger than the SB (6.7 +/- 1.7 mm2 vs. 4.4 +/- 1.4 mm2, p < 0.0001, respectively). When only the MV was considered, the minimum stent area was found in the crush area (rather than the proximal or MV distal stent) in 56%. When both the MV and the SB were considered, the minimum stent area was found at the SB ostium in 68%. The MV minimum stent area measured <4 mm2 in 8% of lesions and <5 mm2 in 20%. For the SB, a minimum stent area <4 mm2 was found in 44%, and a minimum stent area <5 mm2 in 76%, typically at the ostium. "Incomplete crushing"--incomplete apposition of SB or MV stent struts against the MV wall proximal to the carina--was seen in >60% of non-left main lesions. CONCLUSIONS: In the majority of bifurcation lesions treated with the crush technique, the smallest minimum stent area appeared at the SB ostium. This may contribute to a higher restenosis rate at this location.

Multicenter evaluation of carotid artery stenting with a filter protection system.

OBJECTIVES: The aim of this study was to evaluate the feasibility and safety of carotid artery stenting (CAS) with a filter protection system. BACKGROUND: Neurologic events linked to the embolization of particulate matter to the cerebral circulation may complicate CAS. Strategies designed to capture embolic particles during carotid intervention are being evaluated for their efficacy in reducing the risk of these events. METHODS: Between September 1999 and July 2001, a total of 162 patients (164 hemispheres) underwent CAS with filter protection (NeuroShield, MedNova Ltd., Galway, Ireland) according to prospective protocols evaluating the filter system at three institutions. RESULTS: Angiographic success was achieved in 162 of the procedures (99%) and filter placement was successful in 154 (94%) procedures. Carotid access was unsuccessful in two cases (1%) and filter placement in eight cases (5%). Of the latter, five procedures were completed with no protection and three were completed using alternative protection devices. On an intention-to-treat basis, the overall combined 30-day rate of all-stroke and death was 2% (four events: two minor strokes and two deaths). This includes one minor stroke in a patient with failed filter placement and CAS completed without protection. There was one cardiac arrhythmic death and one death from hyperperfusion-related intracerebral hemorrhage. There were no major embolic strokes. CONCLUSIONS: Carotid artery stenting with filter protection is technically feasible and safe. Early clinical outcomes appear to be favorable and need to be confirmed in a larger comparative study.

Intramural coronary delivery of advanced antisense oligonucleotides reduces neointimal formation in the porcine stent restenosis model.

OBJECTIVES: We evaluated the long-term influence of intramural delivery of advanced c-myc neutrally charged antisense oligonucleotides (Resten-NG) on neointimal hyperplasia after stenting in a pig model. BACKGROUND: Neointimal hyperplasia after percutaneous coronary interventions is one of the key components of the restenotic process. The c-myc is a critical cell division cycle protein involved in the formation of neointima. METHODS: In short-term experiments, different doses (from 500 microg to 5 mg) of Resten-NG or saline were delivered to the stent implantation site with an infiltrator delivery system (Interventional Technologies, San Diego, California). Animals were euthanized at 2, 6 and 18 h after interventions, and excised vessels were analyzed for c-myc expression by Western blot. In long-term experiments, either saline or a dose of 1, 5 or 10 mg of Resten-NG was delivered in the same fashion, and animals were euthanized at 28 days after the intervention. RESULTS: Western blot analysis demonstrated inhibition of c-myc expression and was dose dependent. Morphometry showed that the intimal area was 3.88 +/- 1.04 mm(2) in the control. There was statistically significant reduction of intimal areas in the 5 and 10 mg groups (2.01 +/- 0.66 and 1.95 +/- 0.91, respectively, p < 0.001) but no significant reduction in the 1 mg group (2.81 +/- 0.56, p > 0.5) in comparison with control. CONCLUSIONS: This study demonstrated that intramural delivery of advanced c-myc neutrally charged antisense morpholino compound completely inhibits c-myc expression and dramatically reduces neointimal formation in a dose dependent fashion in a porcine coronary stent restenosis model, while allowing for complete vascular healing.

Carotid artery stent placement with distal balloon protection: technical considerations.

BACKGROUND AND PURPOSE: Most neurologic events that complicate the carotid artery stent placement procedure are embolic. Strategies are being developed and evaluated for their ability to minimize the clinical embolic risk. The purpose of this study was to determine the feasibility, safety, and technical considerations of performing carotid artery stent placement with use of a distal balloon antiembolization system. METHODS: Carotid artery stent placement with use of a commercially available distal balloon antiembolization system was performed in 303 patients (325 vessels). Clinical neurologic complications were adjudicated at the time of intervention and at 1 month. RESULTS: Technical success was achieved in all but one case, with reduction of the mean percentage carotid artery stenosis from 79 +/- 9% to 3 +/- 8%. Intolerance to internal carotid artery occlusion occurred in 11 patients (3.6%); in one patient the procedure was aborted, and in 10 the procedures were expeditiously completed with no adverse neurologic events. The 30-day combined rate of all occurrences of stroke and death was 2%. These events included three (0.9%) retinal emboli, three (0.9%) minor strokes, and one (0.3%) fatal stroke from brain hemorrhage, all of which occurred during the procedure with no events occurring after discharge. In addition, two (0.6%) transient ischemic attacks and three (0.9%) reperfusion syndromes occurred, with the patients experiencing complete recovery. CONCLUSION: Carotid artery stent placement with use of the distal balloon protection system is feasible and safe, and the short-term outcomes appear to be favorable. Optimal application of proper technique is important.

Effectiveness of elective stenting of common carotid artery lesions in preventing stroke.

We report our experience with elective stenting of lesions only involving the origin and proximal common carotid arteries. In 37 patients (42 vessels), procedural success was 95% (40 of 42 vessels) with 2 minor strokes (4.70%) and no major strokes. Follow-up for a mean of 24 months showed 1 transient ischemic attack, 2 contralateral minor strokes, 1 cerebral hemorrhage associated with long-term warfarin therapy, and a 5.1% restenosis rate. This technique is an excellent alternative for treating proximal and ostial lesions of the common carotid artery.

Predictors of restenosis after successful carotid artery stenting.

This study was performed to determine the risk factors for restenosis after successful carotid stenting. Of 222 patients who underwent successful carotid stenting, 179 (81%) had a follow-up study (carotid ultrasound and/or angiogram). Restenosis rate was 6.7% (14 of 195) for vessels. By univariate analysis, restenosis rates were significantly different between men and women (4% vs 15.4%, p = 0.018) and age < or =75 versus >75 years (3.8% vs 16%, p = 0.013). By multivariate analysis, older age (odds ratio [OR] 1.107, p = 0.015), female sex (OR 3.519, p = 0.001), implantation of multiple stents (OR 2.363, p = 0.019), and postprocedural percent stenosis (OR 1.067, p = 0.054) were associated with increased incidence of restenosis.

Prognostic significance of cerebrovascular and peripheral arterial disease in patients having percutaneous coronary interventions.

This study shows that cerebrovascular and peripheral arterial diseases frequently co-exist in patients with coronary artery disease who undergo percutaneous coronary interventions. These 2 conditions are associated with adverse in-hospital and 1-year outcomes and independently predict early and 1-year mortality.

Descending necrotizing mediastinitis: a conservative approach.

Descending necrotizing mediastinitis (DNM) is a now-rare complication of dental and pharyngeal infections. Reports in the literature have emphasized the need for early, aggressive surgical intervention. We present a case of DNM with bilateral empyemas that arose secondary to a perforated pharyngeal abscess. The patient was successfully managed conservatively with intravenous antibiotics and intercostal drainage. We conclude that conservative management with antibiotics and image-guided percutaneous pleural drainage may be initially appropriate for the stable patient.

The decline in PCI complication rate: 2003-2006 versus 1999-2002.

INTRODUCTION: Technical improvements permit the performance of percutaneous coronary interventions (PCI) reliably and safely. However, adverse events during such procedures have still not been eliminated. The purpose of this study was to assess the current rates of complications from PCI, as well as any changes from 1999 to 2006. METHODS: Prospectively collected Lenox Hill Hospital data were abstracted from the New York State PCI Report forms and a review of the Quality Improvement office database. The reported complications from 23,399 consecutive PCIs performed during an eight-year period (January 1999 to December 2006) were recorded. The one-month composite endpoint (CEP: death, myocardial infarction, stent thrombosis, stroke, or emergent cardiac surgery within one month of the PCI) and the one-month composite endpoint excluding stent thrombosis (CEPnoST) were evaluated. RESULTS: Complications occurred in 3.36% of PCIs. The following complication rates were found: one month death rate 0.6%, death in the catheterization suite 0.047%, stent thrombosis (one month) 0.53%, presumed stent thrombosis (one month) 0.82%, myocardial infarction (MI: either Q or non-Q wave) 0.74%, emergent cardiac surgery 0.15%, stroke 0.29%, cardiac perforation 0.29%, retroperitoneal bleeding 0.18%, acute renal failure 0.28%, need for hemodialysis 0.17%, CEP 1.8% and CEPnoST 1.58%. When the complication rates from the most recent period (2003-2006) were compared with those from the earlier period (1999-2002), a statistically significant difference was found in total complications, CEP, CEPnoST, stroke, MI, and vascular complications. CONCLUSIONS: Current rates of PCI complications remain low. The overall PCI complication rate was lower during the last four years of the study.

Staged bilateral carotid stenting, an effective strategy in high-risk patients - insights from a prospective multicenter trial.

OBJECTIVE: To prospectively evaluate outcomes of high-risk patients undergoing bilateral carotid artery stenting (CAS). METHODS: A total of 747 patients at increased risk for carotid endarterectomy (CEA) were enrolled in a prospective registry at 47 US sites of the Boston Scientific EPI: A Carotid Stenting Trial for Risk Surgical Patients (BEACH) trial. Among them, 78 (10.4%) patients underwent contralateral CAS > 30 days after the primary CAS procedure. Patients were followed at 1, 6, and 12 months, and annually thereafter for 3 years. The primary endpoint was the cumulative incidence of non Q-wave myocardial infarction within 24 hours, periprocedural (

Carotid artery revascularization in high-surgical-risk patients using the Carotid WALLSTENT and FilterWire EX/EZ: 1-year outcomes in the BEACH Pivotal Group.

OBJECTIVES: The multicenter, single-arm BEACH (Boston Scientific EPI: A Carotid Stenting Trial for High-Risk Surgical Patients) evaluated outcomes in high-surgical-risk patients with carotid artery stenosis treated with the Carotid WALLSTENT plus FilterWire EX/EZ Emboli Protection System (Boston Scientific, Natick, Massachusetts). BACKGROUND: Carotid artery stent (CAS) placement offers a less invasive alternative for high-risk surgical carotid endarterectomy (CEA) patients. METHODS: The trial enrolled 480 pivotal patients who were candidates for carotid revascularization but considered high surgical risk due to pre-specified anatomic criteria and/or medical comorbidities. The primary end point (all stroke, death, or Q-wave myocardial infarction [MI] through 30 days; non-Q-wave MI through 24 h; and ipsilateral stroke or neurologic death through 1 year) was compared with a proportionally weighted objective performance criterion (OPC) of 12.6% for published surgical endarterectomy results in similar patients, plus a pre-specified noninferiority margin of 4%. RESULTS: Among pivotal patients, 41.2% were at high surgical risk due to comorbid risk factors, and 58.8% due to anatomic risk factors; 76.7% were asymptomatic with flow-limiting carotid stenosis >80%. At 1 year, the composite primary end point occurred in 8.9% (40 of 447), with a repeat revascularization rate of 4.7%. With an upper 95% confidence limit of 11.5% for the primary composite end point, the BEACH trial results met the pre-specified criteria for noninferiority relative to the calculated OPC plus noninferiority margin (16.6%) for historical surgical CEA outcomes in similar patients (p < 0.0001 for noninferiority). CONCLUSIONS: The BEACH trial results demonstrate that CAS with the WALLSTENT plus FilterWire embolic protection is non-inferior (equivalent or better than) to CEA at 1-year in high-surgical-risk patients.