Mariusz Trystuła

A Prospective, Multicenter Study of a Novel Mesh-Covered Carotid Stent: The CGuard CARENET Trial (Carotid Embolic Protection Using MicroNet).

OBJECTIVES This study sought to evaluate the feasibility of the CGuard Carotid Embolic Protective Stent system-a novel thin strut nitinol stent combined with a polyethylene terephthalate mesh covering designed to prevent embolic events from the target lesion in the treatment of carotid artery lesions in consecutive patients suitable for carotid artery stenting. BACKGROUND The risk of cerebral embolization persists throughout the carotid artery stenting procedure and remains during the stent healing period. METHODS A total of 30 consecutive patients (age 71.6 ± 7.6 years, 63% male) meeting the conventional carotid artery stenting inclusion criteria were enrolled in 4 centers in Germany and Poland. RESULTS The primary combined endpoint was the procedure success of the CGuard system and the number and volume of new lesions on the ipsilateral side assessed by diffusion-weighted magnetic resonance imaging at 48 h post-procedure and at 30 days. The secondary endpoint was 30-day major adverse cardiac or cerebrovascular events (death, stroke, or myocardial infarction). Protection devices were used in all procedures. Procedure success was 100%, with 0% procedural complications. The 30-day major adverse cardiac or cerebrovascular events rate was 0%. New ipsilateral ischemic lesions at 48 h occurred in 37.0% of patients and the average lesion volume was 0.039 ± 0.08 cm(3). The 30-day diffusion-weighted magnetic resonance imaging showed complete resolution of all but 1 periprocedural lesion and only 1 new minor (0.116 cm(3)) lesion in relation to the 48-h scan. CONCLUSIONS The use of the CGuard system in patients undergoing carotid artery stenting is feasible. In addition, the benefit of using CGuard may extend throughout the stent healing period.

Novel PARADIGM in carotid revascularisation: Prospective evaluation of All-comer peRcutaneous cArotiD revascularisation in symptomatic and Increased-risk asymptomatic carotid artery stenosis using CGuard™ MicroNet-covered embolic prevention stent system.

AIMS Our aim was to determine (1) periprocedural and 30-day clinical safety and efficacy of the CGuard MicroNet-covered embolic prevention carotid stent system (MN-EPS) in routine use for unselected carotid stenosis (CS) patients undergoing CAS, as well as (2) feasibility of MN-EPS post-dilatation optimisation to minimise residual stenosis after CAS. METHODS AND RESULTS This was a non-industry-funded, prospective academic study in all-referrals-tracked symptomatic and asymptomatic CS. In asymptomatic lesions, intervention was mandated only in case of increased stroke risk CS features. There was independent neurologist evaluation before CAS, at 48 hours and 30 days. There was external source data verification, angiographic core lab, and statistical analysis. Over 11 months, 108 referrals were recommended by the NeuroVascular Team for revascularisation: 101 (51-86 years, 55 symptomatic, evolving stroke in nine) underwent 106 (100% MN-EPS use) neuroprotection device-assisted (46% proximal, 54% distal) CAS; CEA was performed in seven. MN-EPS device success was 99.1%. Angiographic diameter stenosis was reduced from 83±9% to 6.7±5% (p<0.001). No MN-EPS foreshortening/elongation occurred (30 mm long was 29.82±0.68 mm; 40 mm long was 39.89±0.59 mm). The periprocedural death/major stroke/MI rate was 0%. One event, with no change in NIHSS or modified Rankin Scale and no clinical sequel, was adjudicated by the clinical events committee as minor stroke (0.9%). By 30 days there were no new events (0%). CONCLUSIONS These increased risk consecutive patient data (1) indicate safety and efficacy of routine MN-EPS use in achieving endovascular reconstruction across all-comer CS lesion subsets, and (2) are consistent with MN-EPS protection against cerebral events extending throughout the stent healing period.

Zotarolimus-eluting stent for the treatment of recurrent, severe carotid artery in-stent stenosis in the TARGET-CAS population.

Purpose To evaluate the safety and efficacy of a balloon-mounted drug-eluting stent (DES) for recurrent carotid in-stent stenosis (ISS). Methods As part of our targeted carotid artery stenting (TARGET-CAS) protocol, neurological and ultrasound evaluations have been performed at 3, 6, and 12 months and then annually since 2001 in all carotid stent patients. For angiographically-confirmed >70% ISS, balloon angioplasty was performed as a first-line treatment. Recurrent ISS was treated with a 4.0-mm zotarolimus-eluting coronary stent (ZES) that was postdilated according to intravascular ultrasound imaging. Among the 1350 neuroprotected CAS procedures performed between January 2001 and March 2011, there were 7 (0.52%) patients (5 men; ages 51–72 years), all neurologically asymptomatic, with >70% recurrent ISS that occurred at 5 to 11 months after the initial balloon angioplasty treatment for ISS. Results ZES implantation under distal embolic protection was technically successful and uncomplicated. Angiographic stenosis was reduced from 84.6%±7.5% to 10.7%±3.6% (p <0.01). In 5 patients with ZES implanted fully within the self-expanding carotid stent, duplex ultrasound follow-up (mean 17 months, range 6–36) revealed no evidence of restenosis or stent fracture/deformation. In the 2 other patients, the ZES had been implanted for distal edge ISS such that the ZES protruded beyond the original carotid stent. This protruding segment of the ZES demonstrated deformation/kinking in both; in one, this led to symptomatic stent occlusion. Conclusion The use of coronary ZES in the treatment of recurrent carotid ISS is feasible and appears effective provided the ZES is placed entirely within the original stent. Placement of a coronary ZES outside the carotid stent scaffold should be avoided.

Myocardial regeneration strategy using Wharton's jelly mesenchymal stem cells as an off-the-shelf 'unlimited' therapeutic agent: results from the Acute Myocardial Infarction First-in-Man Study.

Introduction In large-animal acute myocardial infarction (AMI) models, Whartons jelly (umbilical cord matrix) mesenchymal stem cells (WJMSCs) effectively promote angiogenesis and drive functional myocardial regeneration. Human data are lacking. Aim To evaluate the feasibility and safety of a novel myocardial regeneration strategy using human WJMSCs as a unique, allogenic but immuno-privileged, off-the-shelf cellular therapeutic agent. Material and methods The inclusion criterion was first, large (LVEF ≤ 45%, CK-MB > 100 U/l) AMI with successful infarct-related artery primary percutaneous coronary intervention reperfusion (TIMI ≥ 2). Ten consecutive patients (age 32–65 years, peak hs-troponin T 17.3 ±9.1 ng/ml and peak CK-MB 533 ±89 U/l, sustained echo LVEF reduction to 37.6 ±2.6%, cMRI LVEF 40.3 ±2.7% and infarct size 20.1 ±2.8%) were enrolled. Results 30 × 106 WJMSCs were administered (LAD/Cx/RCA in 6/3/1) per protocol at ≈ 5–7 days using a cell delivery-dedicated, coronary-non-occlusive method. No clinical symptoms or ECG signs of myocardial ischemia occurred. There was no epicardial flow or myocardial perfusion impairment (TIMI-3 in all; cTFC 45 ±8 vs. 44 ±9, p = 0.51), and no patient showed hs-troponin T elevation (0.92 ±0.29 ≤ 24 h before vs. 0.89 ±0.28 ≤ 24 h after; decrease, p = 0.04). One subject experienced, 2 days after cell transfer, a transient temperature rise (38.9°C); this was reactive to paracetamol with no sequel. No other adverse events and no significant arrhythmias (ECG Holter) occurred. Up to 12 months there was one new, non-index territory lethal AMI but no adverse events that might be attributable to WJMSC treatment. Conclusions This study demonstrated the feasibility and procedural safety of WJMSC use as off-the-shelf cellular therapy in human AMI and suggested further clinical safety of WJMSC cardiac transfer, providing a basis for randomized placebo-controlled endpoint-powered evaluation.

Safety of embolic protection device-assisted and unprotected intravascular ultrasound in evaluating carotid artery atherosclerotic lesions.

Summary Background Significant atherosclerotic stenosis of internal carotid artery (ICA) origin is common (5–10% at ≥60 years). Intravascular ultrasound (IVUS) enables high-resolution (120 μm) plaque imaging, and IVUS-elucidated features of the coronary plaque were recently shown to be associated with its symptomatic rupture/thrombosis risk. Safety of the significant carotid plaque IVUS imaging in a large unselected population is unknown. Material/Methods We prospectively evaluated the safety of embolic protection device (EPD)-assisted vs. unprotected ICA-IVUS in a series of consecutive subjects with ≥50% ICA stenosis referred for carotid artery stenting (CAS), including 104 asymptomatic (aS) and 187 symptomatic (S) subjects (age 47–83 y, 187 men). EPD use was optional for IVUS, but mandatory for CAS. Results Evaluation was performed of 107 ICAs (36.8%) without EPD and 184 with EPD. Lesions imaged under EPD were overall more severe (peak-systolic velocity 2.97±0.08 vs. 2.20±0.08m/s, end-diastolic velocity 1.0±0.04 vs. 0.7±0.03 m/s, stenosis severity of 85.7±0.5% vs. 77.7±0.6% by catheter angiography; mean ±SEM; p<0.01 for all comparisons) and more frequently S (50.0% vs. 34.6%, p=0.01). No ICA perforation or dissection, and no major stroke or death occurred. There was no IVUS-triggered cerebral embolization. In the procedures of (i) unprotected IVUS and no CAS, (ii) unprotected IVUS followed by CAS (filters – 39, flow reversal/blockade – 3), (iii) EPD-protected (filters – 135, flow reversal/blockade – 48) IVUS+CAS, TIA occurred in 1.5% vs. 4.8% vs. 2.7%, respectively, and minor stroke in 0% vs. 2.4% vs. 2.1%, respectively. EPD intolerance (on-filter ICA spasm or flow reversal/blockade intolerance) occurred in 9/225 (4.0%). IVUS increased the procedure duration by 7.27±0.19 min. Conclusions Carotid IVUS is safe and, for the less severe lesions in particular, it may not require mandatory EPD use. High-risk lesions can be safely evaluated with IVUS under flow reversal/blockade.

Flow reversal for proximal neuroprotection during endovascular management of critical symptomatic carotid artery stenosis coexisting with ipsilateral external carotid artery occlusion.

Purpose: To report the utility of proximal brain protection by flow reversal in endovascular management of critical internal carotid artery (ICA) stenosis coexisting with ipsilateral external carotid artery (iECA) occlusion. Case Report: Four patients with a symptomatic, critical ICA stenosis (in-stent restenosis in one) and iECA occlusion were admitted for carotid artery stenting (CAS). In all cases, the stenosis severity and high-risk lesion morphology precluded the use of filter protection. The “tailored” CAS algorithm indicated that a proximal anti-embolism system should be used to maximize the potential for effective neuroprotection. The flow reversal system, which consists of an independent guiding sheath balloon positioned in the common carotid artery (CCA) and an iECA balloon-wire, was employed, using the CCA balloon only. The system was well-tolerated, and the CAS procedures were uneventful. Conclusion: Due to a unique design with separate CCA and iECA balloons, the flow reversal system can be used for proximal neuroprotection during CAS in severe, symptomatic ICA lesions coexisting with iECA occlusion.

Treatment strategies in severe symptomatic carotid and coronary artery disease

Summary Coexistent carotid artery stenosis (CS) and multivessel coronary artery disease (CAD) is not infrequent. One in 5 patients with multivessel CAD has a severe CS, and CAD incidence reaches 80% in those referred for carotid revascularization. We reviewed treatment strategies for concomitant severe CS and CAD. We performed a literature search (MEDLINE) with terms including carotid artery stenting (CAS), coronary artery bypass grafting (CABG), carotid endarterectomy (CEA), stroke, and myocardial infarction (MI). The main therapeutic option for CS-CAD has been (simultaneous or staged) CEA-CABG. This, however, is associated with a high risk of MI (in those with CEA prior to CABG) or stroke (CABG prior to CEA), and the cumulative major adverse event rate (MAE – death, stroke or MI) reaches 10–12%. With increasing adoption of CAS, a sequential strategy of CAS followed by CABG has emerged. Registries (usually single-centre) indicate an MAE rate of ≈7% for CAS followed by CABG (frequently after >30 days, due to double antiplatelet therapy). Recently, 1-stage CAS-CABG has been introduced. This involves different antiplatelet regimens and, in some centers, preferred off-pump CABG, with a cumulative MAE of 1.4–4.5%. No randomized trial comparing different treatment strategies in CS-CAD has been conducted, and thus far reported series are prone to selection/reporting bias. In addition to the established surgical treatment (CEA-CABG, sequential/simultaneous), hybrid revascularization (CAS-CABG) is emerging as a viable therapeutic option. Larger, preferably multi-centre, studies are required before this can become widely applied.

Carotid artery stenting according to the “tailored CAS” algorithm performed in the very elderly patients: The thirty day outcome

To assess safety and efficacy of carotid artery stenting (CAS) according to “tailored—CAS” algorithm in the elderly (≥75 years) in relation to younger patients.

Simultaneous vertebral and subclavian artery stenting

Introduction Vertebrobasilar territory ischemia leads to disabling neurological symptoms and may be caused both by vertebral artery (VA) and subclavian artery (SA) stenosis. The coexisting symptomatic ipsilateral VA and proximal SA stenosis should be considered as a true bifurcation lesion for percutaneous treatment. Aim To evaluate the safety and efficacy of simultaneous angioplasty of vertebral and subclavian stenosis. Material and methods Fifteen patients (age 69.5 years, 46.7% men, all symptomatic from posterior circulation (history of stroke, transient ischemic attack, chronic ischemia symptoms)) were scheduled for simultaneous SA/VA angioplasty. Clinical and duplex ultrasound follow-up was conducted 1, 6 and 12 months after the procedure. Results The technical success rate was 100%. Single balloon-mounted stent angioplasty was performed for all VAs and for 13 (86.7%) SAs. In 4 cases a simultaneous radial and femoral approach was required. The mean North American Symptomatic Carotid Endarterectomy Trial (NASCET) VA stenosis was reduced from 88.7 ±9.7% to 5.7 ±6.8% and SA stenosis from 80 ±12.2% to 11 ±12.3% (p < 0.01). No periprocedural death, stroke, myocardial infarction or transient ischemic attack occurred. During follow-up (range: 6–107 months) in 10 of 15 (66.7%) patients relief of chronic ischemic symptoms was observed. No stroke/TIA occurred. One cardiovascular and 2 non-cardiovascular deaths were recorded. There was 1 symptomatic vertebral and 1 subclavian in-stent restenosis, and 2 cases of asymptomatic VA in-stent occlusion occurred. Conclusions Simultaneous vertebral and subclavian artery stenting is safe and effective. The restenosis rate remains at an acceptable level and it may be treated successfully with drug-eluting balloon angioplasty. In selected patients a dual radial and femoral approach may facilitate the procedure.

Mesh-covered (Roadsaver) stent as a new treatment modality for symptomatic or high-risk carotid stenosis

Introduction Prevention of periprocedural stroke has a crucial role in carotid artery stenting (CAS) procedures. Aim To assess retrospectively 30-day safety and effectiveness of 41 procedures of internal and common carotid artery stenting using the Roadsaver double nitinol layer micromesh stent in 40 non-consecutive patients with symptomatic or high-risk carotid artery stenosis. Material and methods The patients were men (n = 31) and women (n = 9); mean age was 67.8 ±7.9 years. Femoral access was used in 39 cases, whereas radial access was used in 2. Proximal (n = 27) or distal (n = 14) embolic neuroprotection was used. Results The Roadsaver stents (nominal diameter 7, 8 or 9 mm, length 25 or 30 mm) were implanted successfully in all cases. One minor stroke occurred after common carotid artery intubation with a guiding catheter (before stent deployment) and one transient postprocedural ischemic attack (TIA) of the ipsilateral cerebral hemisphere was observed. Internal/common carotid artery stenosis severity was evaluated by duplex Doppler. Maximal peak systolic velocity (PSV) before CAS was in the range: 2.0–7.0 m/s, mean: 3.9 ±1.0 m/s, at 24–48 h after stenting mean PSV was 1.1 ±0.4 m/s (p < 0.05), and at 30 days 1.1 ±0.3 m/s (p < 0.05). Maximal end-diastolic velocity (EDV) was 0.85–3.5 m/s, mean 1.4 ±0.5 m/s, at 24–48 h after stenting mean EDV was 0.3 ±0.1 m/s (p < 0.05), and at 30 days 0.4 ±0.1 m/s (p < 0.05). No restenosis or thrombosis was observed. Angiographic stenosis decreased from 82.9 ±9.1% (range: 61–97%) to 19.3 ±7.3% (range: 0–34%) (p < 0.05). Conclusions The CAS using the Roadsaver stent seems to be safe and effective. Further studies involving larger patient populations and longer follow-up are needed.