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Purpose: Recent evidence shows that blood biomarkers, in isolation, are largely ineffective in risk stratification of carotid atherosclerotic plaque (CS) symptomatic transformation. Stenosis degree is a poor marker of symptom risk while plaque morphology may play a role. Intravascular ultrasound (IVUS) provides high-resolution (axial ≤0.12mm for 20MHz transducer) imaging, but conventional phenotypic virtual histology (VH-IVUS) plaque classification poor between-center/-observer reproducibility limits any wider applicability. Moreover, conventional VH-IVUS, addressing total content of eg necrotic core (NC), does not discriminate focal vs. dissociated NC that is relevant to rupture risk. We investigated whether quantitative measures of key plaque components implicated in rupture risk are related to levels of several circulating biomarkers.Methods: We developed a novel software-based algorithm for detailed, fully-quantitative VH-IVUS analysis of key plaque components known for their role in plaque rupture/thrombosis. In 21 plaques we validated inter-transducer (2 transducers) and inter-observer (3 observers) reproducibility of qVH-IVUS analysis including minimal fibrous cap (FC) thickness, and peak confluent NC area, thickness and arc. Next we employed our qVH-IVUS algorithm to evaluate CS lesions in 252 consecutive patients (age 47–83, 63.4% men, h/o CS-attributable symptoms in 50.3%) presenting for potential CS revascularization. Finally, in the first 200 subjects we determined the levels of a panel of biomarkers and preformed regression analysis in search for quantitative CS morphology/biomarker associations.Results: qVH-IVUS revealed significant differences in minimal FC thickness (0.41±0.04 v 0.34±0.05 v 0.16±0.02 v 0.19±0.03mm), peak confl NC area (3.0±0.2 v 2.5±0.3 v 4.4±0.4 v 3.4±0.5mm2), arc (87.1±6 v 67.2±6 v 121.6±9 v 94.0±9deg) and thickness (0.88±0.04 v 1.07±0.07 v 1.34±0.06 v 1.16±0.11 mm); data for asympt CS in absence of contralat symptoms, asympt CS in presence of contralat symptoms, recently symptomatic and remotely symptomatic CS, p<0.001 for all.While hsCRP was not correlated with min FC (r=-0.24, p=0.74) or NC area (r=0.05, p=0.48), TIMP correlated with min FC (r=0.34, p=0.001). Modest though highly significant correlations were identified between Lp-PLA2 and confl NC area (r=0.3, p=0.0001), HDL and confl NC thckn (r=-0.21, p=0.002). Fibrinogen level correlated with % plaque fibrotic content (r=0.19, p=0.008).Conclusion: These findings provide novel insights into circulating biomarker/quantitative plaque morphology associations that may be relevant to plaque biology and risk. [ABSTRACT FROM AUTHOR]

Competing Interests: PM has proctored and/or consulted for Abbott Vascular, Balton, Gore, InspireMD, and Medtronic; he has served as the Polish Cardiac Society Board Representative for Stroke and Vascular Interventions and serves on the ESC Stroke Council Scientific Documents Task Force. PM is Co-PI of the CGuardians FDA IDE Trial. Other authors declare no conflict of interest.

Introduction: Acute carotid-related stroke (CRS), with its large thrombo-embolic load and large volume of affected brain tissue, poses significant management challenges. First generation (single-layer) carotid stents fail to insulate the athero-thrombotic material; thus they are often non-optimized (increasing thrombosis risk), yet their use is associated with a significant (20-30%) risk of new cerebral embolism., Aim: To evaluate, in a multi-center multi-specialty investigator-initiated study, outcomes of the MicroNET-covered (cell area ≈ 0.02-0.03 mm 2 ) carotid stent (CGuard, InspireMD) in consecutive CRS patients eligible for emergency recanalization. Treatment, other than study device use, was according to center/operator routine., Material and Methods: Seventy-five patients (age 40-89 years, 26.7% women) were enrolled in 7 interventional stroke centers., Results: The median Alberta Stroke Program Early CT Score (ASPECTS) was 9 (6-10). Study stent use was 100% (no other stent types implanted); retrograde strategy predominated (69.2%) in tandem lesions. Technical success was 100%. Post-dilatation balloon diameter was 4.0 to 8.0 mm. 89% of patients achieved final modified Thrombolysis in Cerebral Infarction (mTICI) 2b-c/3. Glycoprotein IIb/IIIa inhibitor use as intraarterial (IA) bolus + intravenous (IV) infusion was an independent predictor of symptomatic intracranial hemorrhage (OR = 13.9, 95% CI: 5.1-84.5, p < 0.001). The mortality rate was 9.4% in-hospital and 12.2% at 90 days. Ninety-day mRS0-2 was 74.3%, mRS3-5 13.5%; stent patency was 93.2%. Heparin-limited-to-flush predicted patency loss on univariate (OR = 14.3, 95% CI: 1.5-53.1, p < 0.007) but not on multivariate analysis. Small-diameter balloon/absent post-dilatation was an independent predictor of stent patency loss (OR = 15.2, 95% CI: 5.7-73.2, p < 0.001)., Conclusions: This largest to-date study of the MicroNET-covered stent in consecutive CRS patients demonstrated a high acute angiographic success rate, high 90-day patency and favorable clinical outcomes despite variability in procedural strategies and pharmacotherapy (SAFEGUARD-STROKE NCT05195658)., Competing Interests: PM has been proctoring and/or consulting for Abbott Vascular, Balton, Gore, InspireMD, and Medtronic. PM has served as the Polish Cardiac Society Board Representative for Stroke and Vascular Interventions and serves on the ESC Stroke Council Scientific Documents Task Force. PM is Global Co-Principal Investigator in the CGUARDIANS FDA IDE Trial of the MicroNET-covered carotid stent system. HS has proctored and advised to manufacturers of interventional cardiovascular medicine equipment and devices. IQG was the Principal Investigator on the first study of thrombus aspiration in acute ischemic stroke and has proctored and advised to neurointerventional equipment and device manufacturers. IQG is Vice-President of the World Federation for Interventional Stroke Treatment (WIST). The other authors report no conflicting interests., (Copyright: © 2024 Termedia Sp. z o. o.)

Cardio-cerebral infarction (CCI) is a term coined to describe concomitant myocardial infarction and acute ischemic stroke. Acute myocardial infarction and stroke, as separate events, constitute some of the most important causes for disability and mortality in aging societies. Stroke can either occur simultaneously with myocardial infarction or become a serious complication of myocardial infarction and/or its treatment. The frequency of CCI has been reported at a 0.009% incidence rate in stroke patients and is associated with an extremely high mortality. Because of the rare occurrence of CCI, there are currently no guidelines for assessing its diagnosis and optimal treatment. Therefore, currently, the management of CCI cases needs to be individualized. Hopefully, in the future, the results of large clinical trials or prospective registries are expected to enhance our understanding of managing concomitant acute MI and stroke. In this review we have focused on the current literacy in the diagnosis and treatment of CCIs. The paper illustrates potential distinct scenarios of CCI through the analysis of three patient cases (Fig. 5, Ref. 65). Text in PDF www.elis.sk Keywords: myocardial infarction, stroke, cardio-cerebral infarction, carotid artery stenting, cardiac surgery.

Introduction: Today, endovascular treatment (EVT) is the therapy of choice for strokes due to acute large vessel occlusion, irrespective of prior thrombolysis. This necessitates fast, coordinated multi-specialty collaboration. Currently, in most countries, the number of physicians and centres with expertise in EVT is limited. Thus, only a small proportion of eligible patients receive this potentially life-saving therapy, often after significant delays. Hence, there is an unmet need to train a sufficient number of physicians and centres in acute stroke intervention in order to allow widespread and timely access to EVT., Aim: To provide multi-specialty training guidelines for competency, accreditation and certification of centres and physicians in EVT for acute large vessel occlusion strokes., Material and Methods: The World Federation for Interventional Stroke Treatment (WIST) consists of experts in the field of endovascular stroke treatment. This interdisciplinary working group developed competency - rather than time-based - guidelines for operator training, taking into consideration trainees' previous skillsets and experience. Existing training concepts from mostly single specialty organizations were analysed and incorporated., Results: The WIST establishes an individualized approach to acquiring clinical knowledge and procedural skills to meet the competency requirements for certification of interventionalists of various disciplines and stroke centres in EVT. WIST guidelines encourage acquisition of skills using innovative training methods such as structured supervised high-fidelity simulation and procedural performance on human perfused cadaveric models., Conclusions: WIST multispecialty guidelines outline competency and quality standards for physicians and centres to perform safe and effective EVT. The role of quality control and quality assurance is highlighted., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Termedia Sp. z o. o.)

Introduction: It has been suggested that infarct-related artery (IRA) atherosclerosis progression after stem cell transcoronary administration might represent a stem-cell mediated adverse effect., Aim: To evaluate, using conventional (quantitative coronary angiography, QCA, intravascular ultrasound - IVUS) and novel (quantitative virtual histology - qVH) tools, evolution of IRA atherosclerosis following transcoronary stem cell transfer., Material and Methods: QCA, IVUS, VH-IVUS and qVH were performed in 22 consecutive patients (4 women) aged 59 years (data provided as median) undergoing a distal-to-stent infusion of 2.21 × 10 6 CD34 + CXCR4 + autologous bone marrow cells via a cell delivery-dedicated perfusion catheter at anterior AMI day 7. Imaging was repeated at 12 months. This was a substudy of Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial (NCT00316381)., Results: 18.2% subjects showed absence of distal-to-stent angiographic/IVUS atherosclerotic lesion(s) at baseline and no new lesion(s) at 12-months. In the remaining cohort, there were 28 lesions by QCA (32 by IVUS) at baseline and no new lesion(s) at follow-up. Three fibroatheromas evolved (2 to calcified fibroatheroma and 1 to a fibrocalcific lesion); other plaques maintained their stable (low-risk) phenotypes. Diameter stenosis of QCA-identified lesions was 29.5 vs. 26.5% ( p = 0.012, baseline vs. 12-months). Gray-scale IVUS showed reduction in area stenosis (33.8 vs. 31.0%, p = 0.004) and plaque burden (66.27 vs. 64.56%, p = 0.009) at 12-months. Peak fibrotic plaque content increased from 70.41% to 75.0% ( p = 0.004). qVH peak confluent necrotic core area and minimal fibrous cap thickness remained stable (0.64 vs. 0.59 mm 2 , p = 0.290, and 0.15 vs. 0.16 mm, p = 0.646)., Conclusions: This study, using a range of classic and novel imaging techniques, indicates lack of any stimulatory effect of transcoronary stem cell transfer on coronary atherosclerosis. Whether, and to what extent, a moderate reduction in plaque burden and stenosis severity at 12-months results from optimized pharmacotherapy and/or stem cell transfer requires further elucidation., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Termedia Sp. z o. o.)

Introduction: Recent analysis from CHART-1 study indicated that the therapeutic effects of trans-endocardial cardiopoetic cell transplantation in chronic ischemic heart failure (iCHF) may be lost with an increasing number of injections perfomed to deliver therapeutic cells., Aim: To evaluate global and regional contractility and diastolic function of the left ventricle of patients with iCHF who received trans-endomyocardial cardiopoietic stem cells (CSCs) delivery or sham procedures., Material and Methods: The study included patients (mean age: 60.8 ±7.1 years) with iCHF (left ventricular ejection fraction (LVEF) < 35%) and a history of hospitalization for worsening heart failure within 12 months despite optimal medical therapy. The patients underwent transmyocardial CSCs transplantation using perforated needle technique or a sham procedure. The wall motion score index (WMSI), LVEF, transmitral E-velocity, E-wave deceleration time, E/A-ratio, and E/e'-mean value were measured with two-dimensional echocardiography on days 1 and 30., Results: A total of 170 segments were analyzed, including 48 targeted segments where 92 injections of 0.5 ml of CSCs were performed. In the transendocardial injections cohort, a decrease in regional contractility was observed in 30.6% (26/85) and 18.9% (16/85) of the segments on days 1 and 30, respectively. This was accompanied by an increase in WMSI by 0.32 ±0.06 and 0.19 ±0.18 (day 1, p = 0.02, day 30, p = 0.03) and a reduction in LVEF (-3.15 ±1.23%, p = 0.065)., Conclusions: Transendocardial injections performed to deliver therapeutic cells were associated with myocardial injury. This adverse effect remained, albeit at a lesser degree, at 30-days. Mechanical injury with trans-endocardial delivery of progenitor cells using the "needle technique" may counterbalance, at least in part, any cell-related benefit(s)., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 Termedia Sp. z o. o.)

Intoduction: Despite a growing understanding of the role played by plaque morphology, the degree of carotid lumen reduction remains the principle parameter in decisions on revascularization in symptomatic and asymptomatic patients. Computed tomography angiography (CTA) is a widely used guideline-approved imaging modality, with "percent stenosis" commonly calculated as %area reduction (area stenosis - AS)., Aim: We evaluated the impact of the non-linear relationship between diameter stenosis (DS) and AS (area = π • (diameter/2) 2 , so that in concentric lesions 51%AS is 30%DS and 75%AS is 50%DS) on stenosis severity misclassification using calculation of area reduction., Material and Methods: CTA and catheter quantitative angiography (cQA) were performed in 300 consecutive patients referred to a tertiary vascular centre for potential carotid revascularization (age: 47-83 years, 33.7% symptomatic, 36% female; referral stenosis of ≥ "50%"). CTA-AS was determined by agreement of 2 experienced radiologists; cQA-DS (pivotal trials standard reference, NASCET method) was calculated by agreement of 2 corelab analysts., Results: For symptomatic lesion thresholds, CTA-AS-based calculation reclassified 76% of "< 50%" cQA-DS measurements to the "50-69%" group, and 58% of "50-69%" measurements to the "≥ 70%" group. For asymptomatic lesion thresholds, 78% of "< 60%" cQA-DS measurements were reclassified to the "60-79%" group, whereas 42% of "60-79%" cQA measurements crossed to the "≥ 80%" class. Overall, employing CTA-AS instead of cQA-DS enlarged the "60-79%" and "≥ 80%" lesion severity classes 1.6- and 5.8-fold, respectively, whereas the "≥ 70%" class increased 4.15-fold., Conclusions: Replacing the pivotal carotid trials reference standard cQA-DS "%stenosis" measurement with CTA-AS-based "%stenosis" results in a large-scale lesion/patient erroneous gain of an "indication" to revascularization or migration to a higher revascularization indication class. In consequence, unnecessary carotid procedures may be performed in the absence of cQA verification. Until guidelines rectify the "%stenosis" measurement methods with different guideline-approved imaging modalities (and, where needed, re-adjust decision thresholds), CTA-AS measurement should not be used as a basis for carotid revascularization., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Termedia Sp. z o. o.)

Introduction: Carotid artery stenting (CAS) using conventional (single-layer) stents is associated with worse clinical outcomes in diabetes mellitus (DM) vs. non-DM patients: an effect driven largely by lesion-related adverse events. CAS outcomes with MicroNet-covered stents (MCS) in diabetic patients have not been evaluated., Aim: To compare short- and long-term clinical outcomes and restenosis rate in DM vs. non-DM patients with carotid stenosis treated using MCS., Materials and Methods: In a prospective study in all-comer symptomatic and increased-stroke-risk asymptomatic carotid stenosis, 101 consecutive patients (age 51-86 years, 41% diabetics) underwent 106 MCS-CAS. Clinical outcomes and duplex ultrasound velocities were assessed periprocedurally and at 30 days/12 months., Results: Baseline characteristics of DM vs. non-DM patients were similar except for a higher prevalence of recent cerebral symptoms in DM. Type 1 and type 1+2 plaques were more prevalent in DM patients (26.7% vs. 9.8%, p = 0.02; 62.2% vs. 37.7%, p = 0.01). Proximal embolic protection was more prevalent in DM (60% vs. 36%; p = 0.015). 30-day clinical complications were limited to a single periprocedural minor stroke in DM (2.4% vs. 0%, p = 0.22). 12-month in-stent velocities and clinical outcomes were not different (death rate 4.8% vs. 3.3%; p = 0.69; no new strokes). Restenosis rate was not different (0% vs. 1.7%, p = 0.22)., Conclusions: MCS may offset the adverse impact of DM on periprocedural, 30-day, and 12-month clinical complications of CAS and minimize the risk of in-stent restenosis. In this increased-stroke-risk cohort, adverse event rate was low both in DM and non-DM. Further larger-scale clinical datasets including extended follow-ups are warranted., Competing Interests: PM consulted for Abbot Vascular, InspireMD, and Medtronic and is a proctor for InspireMD and Medtronic. PM was Co-Principal Investigator in the CGuard CARENET study and is currently Co-Principal Investigator in the CGUARDIANS FDA-IDE Trial. Other authors have no conflicts of interest to declare., (Copyright © 2022 Adam Mazurek et al.)

Background: Single-cohort studies suggest that second-generation stents (SGS; “mesh stents”) may improve carotid artery stenting (CAS) outcomes by limiting peri- and postprocedural cerebral embolism. SGS differ in the stent frame construction, mesh material, and design, as well as in mesh-to-frame position (inside/outside). Objectives: To compare clinical outcomes of SGS in relation to first-generation stents (FGSs; single-layer) in CAS. Methods: We performed a systematic review and meta-analysis of clinical studies with FGSs and SGS (PRISMA methodology, 3302 records). Endpoints were 30-day death, stroke, myocardial infarction (DSM), and 12-month ipsilateral stroke (IS) and restenosis (ISR). A random-effect model was applied. Results: Data of 68,422 patients from 112 eligible studies (68.2% men, 44.9% symptomatic) were meta-analyzed. Thirty-day DSM was 1.30% vs. 4.11% (p < 0.01, data for SGS vs. FGS). Among SGS, both Casper/Roadsaver and CGuard reduced 30-day DSM (by 2.78 and 3.03 absolute percent, p = 0.02 and p < 0.001), whereas the Gore stent was neutral. SGSs significantly improved outcomes compared with closed-cell FGS (30-day stroke 0.6% vs. 2.32%, p = 0.014; DSM 1.3% vs. 3.15%, p < 0.01). At 12 months, in relation to FGS, Casper/Roadsaver reduced IS (−3.25%, p < 0.05) but increased ISR (+3.19%, p = 0.04), CGuard showed a reduction in both IS and ISR (−3.13%, −3.63%; p = 0.01, p < 0.01), whereas the Gore stent was neutral. Conclusions: Pooled SGS use was associated with improved short- and long-term clinical results of CAS. Individual SGS types, however, differed significantly in their outcomes, indicating a lack of a “mesh stent” class effect. Findings from this meta-analysis may provide clinically relevant information in anticipation of large-scale randomized trials., Competing Interests: Kenneth Rosenfield reports receiving fees for serving on advisory boards from Abbott Vascular, Cardinal Health, Surmodics, Inari Medical, Volcano/Philips, and Proteon; receiving fees and stock options for serving on advisory boards from Cruzar Systems, Valcare, and Eximo; receiving stock options for serving on advisory boards from Capture Vascular, Shockwave, Micell, Endospan, and Silk Road Vascular; receiving stock options for serving on the advisory boards of and the holding of equity positions in Contego, Access Vascular, and MD Insider; holding stock/stock options in Embolitech, Janacare, Primacea, and PQ Bypass; receipt of a future payout from a previous equity position in Vortex; and receiving grant support paid to his institution from Abbott Vascular, Atrium/Maquet, and Lutonix/Bard. David Christopher Metzger is Co- Principal Investigator in the CGUARDIANS FDA-IDE Trial. Adnan H. Siddiqui has consulted for Amnis Therapeutics Ltd, Cerebrotech Medical, Systems Inc, CereVasc LLC, Claret Medical Inc, Codman, Corindus Inc, GuidePoint Global Consulting, Medtronic (Formerly Covidien), MicroVention, Neuravi, Penumbra, Pulsar Vascular, Rapid Medical, Rebound Therapeutics Corporation, Silk Road Medical, Stryker, The Stroke Project Inc, Three Rivers Medical Inc, W.L. Gore & Associates, and is a Board Member of Intersocietal Accreditation Commission. He has been Principal Investigator and/or served on Steering Committees for: Codman & Shurtleff, LARGE Trial, Covidien (Now Medtronic), SWIFT PRIME and SWIFT DIRECT Trials; MicroVention, FRED Trial, CONFIDENCE Study, MUSC, POSITIVE Trial; Penumbra, 3D Separator Trial, COMPASS Trial, INVEST Trial. AHS has financial interests in BuffaloTechnology Partners Inc, Cardinal, International Medical Distribution Partners, Medina Medical Systems, Neuro Technology Investors, StimMed, and Valor Medical. Piotr Pieniazek has proctored and/or consulted for Terumo, Boston Scientific and Balton. Joachim Schofer has been Co-Principal Investigator in the CARENET Trial. Andrej Schmidt has consulted for Abbott Vascular, BD, Cook and Medtronic. Piotr Musialek has proctored and/or consulted for Abbott Vascular, InspireMD, and Medtronic. PM is Co- Principal Investigator in the CGUARDIANS FDA-IDE Trial and has been Co-Principal Investigator in the CARENET Trial; he is Principal Investigator in a series of Investigator-Initiated studies including PARADIGM/PARADIGM-Extend (NCT04271033), FLOW-GUARD (NCT04461717), OPTIMA (NCT04234854), TOP-GUARD (NCT0454738), C-HEAL (NCT04434456), SIM-GUARD (NCT04973579) and SAFEGUARD-STROKE (NCT05195658). PM is the Polish Cardiac Society Board Representative for Stroke and Vascular Interventions and serves on the European Society of Cardiology (ESC) Stroke Council Scientific Documents Task Force and on ESC Research and Grants Committee. Other author declare no conflict of interest.

Competing Interests: Funding Support and Author Disclosures This work was supported by the John Paul II Hospital in Krakow Research Fund. Dr Musialek has received proctoring and consulting fees from Abbott Vascular, InspireMD, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Optimal management of patients with internal carotid artery (ICA) stenosis concurrent with severe cardiac disease remains undefined. The aim of this study is to evaluate the safety and feasibility of the one-day, sequential approach by carotid artery stenting (CAS) immediately followed by cardiac surgery. The study included 70 consecutive patients with symptomatic > 50% or ⩾ 80% asymptomatic ICA stenosis coexisting with severe coronary/valve disease, who underwent one-day, sequential CAS + cardiac surgery. The majority of patients (85.7%) had CSS class III or IV angina and 10% had non-ST elevation myocardial infarction. The EuroSCORE II risk was 2.4% (IQR 1.69-3.19%). All CAS procedures were performed according to the 'tailored' algorithm with a substantial use of proximal neuroprotection devices of 44.3%. Closed-cell (75.7%) and mesh-covered (18.6%) stents were implanted in most cases. The majority of patients underwent isolated coronary artery bypass grafting (88.6%) or isolated valve replacement (7.1%). No major adverse cardiac and cerebrovascular events (MACCE) occurred at the CAS stage. There were three (4.3%) perioperative MACCE: one myocardial infarction and two deaths. All MACCE were related to cardiac surgery and were due to the high surgical risk profile of the patients. Up to 30 days, no further MACCE were observed. No perioperative or 30-day neurological complications occurred. In this patient series, one-day, sequential CAS and cardiac surgery was relatively safe and did not result in neurological complications. Thus, a strategy of preoperative CAS could be considered for patients with severe or symptomatic ICA stenosis who require urgent cardiac surgery.

Introduction: Drug-eluting stents of the first (DES I) and second generation (DES II) proved superior to bare metal stents (BMS) in the coronary territory. However, there are limited data on whether they have any advantage over BMS in vertebral artery stenosis (VAS)., Aim: To compare outcomes of DES (DES I, DES II) and BMS in the treatment of symptomatic extracranial VAS., Material and Methods: During 13-year study period (2003-2016), 392 consecutive patients underwent VAS angioplasty in 428 arteries, including implantation of 148 DES (DES I: 21; DES II: 127 lesions), and 280 BMS., Results: The technical success rates for DES and BMS groups were 96.7% and 94.6% ( p = 0.103), with similar periprocedural complication rates (1.4% vs. 2.2%; p = 0.565). VAS degree was reduced from 86 ±9.7 to 2.7 ±5.0% in DES ( p < 0.001) and from 84.1 ±9.4 to 4.3 ±6.9% in BMS ( p < 0.001). Angiography confirmed in-stent restenosis/occlusion (ISR/ISO) 50-99% in 53 (14.2%) and 21 (5.6%) out of 373 patients (409 arteries) with at least 6-month follow-up. ISR/ISO rates were similar in DES vs. BMS (22.8% vs. 19.4%; p = 0.635), as well as in DES I vs. DES II (6/19; 31.6% vs. 25/92; 27.2%, p = 0.325). Stainless steel (24/135; 17.8%) and cobalt-chromium (23/121;19%) BMS had significantly lower incidence of ISR/ISO, as compared to platinum-chromium (7/18; 38.9%), p = 0.034. ISR/ISO was associated with age ( p = 0.01) and CRP level > 5 mg/l ( p = 0.043), while greater stent length was associated with ISR only in the DES group ( p = 0.024)., Conclusions: Our results do not support significant differences in ISR/ISO rates between DES and BMS, although differences between particular stent types and ISR rates require further investigation., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2019 Termedia Sp. z o. o.)

Introduction: In large-animal acute myocardial infarction (AMI) models, Wharton's 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 × 10(6) 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.

We present a case of a 73-year-old man with critical bilateral internal carotid artery stenosis, recent right-hemisphere stroke and severe peripheral artery disease in whom right internal carotid artery stenting (RICA-CAS) was performed successfully via a right transradial approach.

Background and Purpose: Several circulating biomarkers have been implicated in carotid atherosclerotic plaque rupture and thrombosis; however, their clinical utility remains unknown. The aim of this study was to determine the role of a large biomarker panel in the discrimination of symptomatic (S) vs. asymptomatic (A/S) subjects in a contemporary population with carotid artery stenosis (CS)., Methods: Prospective sampling of circulating cytokines and blood lipids was performed in 300 unselected, consecutive patients with ≥50% CS, as assessed by duplex ultrasound (age 47-83 years; 110 with A/S and 190 with S) who were referred for potential CS revascularization., Results: CS severity and pharmacotherapy did not differ between the A/S and S patients. The median values of total cholesterol, low-density lipoprotein cholesterol, and lipoprotein(a) did not differ, but high-density lipoprotein (HDL) cholesterol was significantly higher (p<0.001) and triglycerides were lower (p=0.03) in the A/S-CS group than in the S-CS group. Interleukin-6 (IL-6) and high-sensitivity C-reactive protein were higher (p=0.04 and p=0.07, respectively) in the S-CS group. Circulating visfatin, soluble CD 40 receptor ligand, soluble vascular cell adhesion molecule, leptin, adiponectin, IL-1β, IL-8, IL-18, monocyte chemoattractant protein-1, myeloperoxidase, matrix metalloproteinases-8, -9, and -10, and fibrinogen were similar, but tissue inhibitor of matrix metalloproteinases-1 (TIMP) was reduced in S-CS compared to A/S-CS (p=0.02). Nevertheless, incorporation of TIMP and IL-6 did not improve the HDL-cholesterol receiver operating characteristics for S-CS status prediction. S-CS status was unrelated to angiographic stenosis severity or plaque burden, as assessed by intravascular ultrasound (p=0.16 and p=0.67, respectively). Multivariate logistic regression analysis revealed low HDL-cholesterol to be the only independent predictor of CS symptoms, with an odds ratio of 1.81 (95% confidence interval=1.15-2.84, p=0.01) for HDL <1.00 mmol/L (first quartile) vs. >1.37 (third quartile). In S-CS, osteoprotegerin and lipoprotein-associated phospholipase A2 (Lp-PLA2) were elevated in those with recent vs. remote symptoms (p=0.01 and p=0.02, respectively)., Conclusions: In an all-comer CS population on contemporary pharmacotherapy, low HDL-cholesterol (but not other previously implicated or several novel circulating biomarkers) is an independent predictor of S-CS status. In addition, an increase in circulating osteoprotegerin and Lp-PLA2 may transiently indicate S transformation of the carotid atherosclerotic plaque.

Background: Effective progenitor cell recruitment to the ischemic injury zone is a prerequisite for any potential therapeutic effect. Cell uptake determinants in humans with recent myocardial infarction are not defined. We tested the hypothesis that myocardial uptake of autologous CD34(+) cells delivered via an intracoronary route after recent myocardial infarction is related to left ventricular (LV) ejection fraction (LVEF) and infarct size., Methods and Results: Thirty-one subjects (age, 36-69 years; 28 men) with primary percutaneous coronary intervention-treated anterior ST-segment-elevation myocardial infarction and significant myocardial injury (median peak troponin I, 138 ng/dL [limits, 58-356 ng/dL]) and sustained LVEF depression at ≤45% were recruited. On day 10 (days 7-12), 4.3×10(6) (0.7-9.9×10(6)) (99m)Tc-extametazime-labeled autologous bone marrow CD34(+) cells (activity, 77 MBq [45.9-86.7 MBq]) were administered transcoronarily (left anterior descending coronary artery). (99m)Tc-methoxyisobutyl isonitrile (99(m)Tc-MIBI) single-photon emission computed tomography before cell delivery showed 7 (2-11) (of 17) segments with definitely abnormal/absent perfusion. Late gadolinium-enhanced infarct core mass was 21.7 g (4.4-45.9 g), and infarct border zone mass was 29.8 g (3.9-60.2 g) (full-width at half-maximum, signal intensity thresholding algorithm). One hour after administration, 5.2% (1.7%-9.9%) of labeled cell activity localized in the myocardium (whole-body planar γ scan). Image fusion of labeled cell single-photon emission computed tomography with LV perfusion single-photon emission computed tomography or with cardiac magnetic resonance infarct imaging indicated cell uptake in the peri-infarct zone. Myocardial uptake of labeled cells activity correlated in particular with late gadolinium-enhanced infarct border zone mass (r=0.84, P<0.0001) and with peak troponin I (r=0.76, P<0.001); it also correlated with severely abnormal/absent perfusion segment number (r=0.45, P=0.008) and late gadolinium-enhanced infarct core (r=0.58 and r=0.84, P<0.0001) but not with echocardiography LVEF (r=-0.07, P=0.68) or gated single-photon emission computed tomography LVEF (r=-0.28, P=0.16). The correlation with cardiac magnetic resonance imaging-LVEF was weak (r=-0.38; P=0.04)., Conclusions: This largest human study with labeled bone marrow CD34(+) cell transcoronary transplantation after recent ST-segment-elevation myocardial infarction found that myocardial cell uptake is determined by infarct size rather than LVEF and occurs preferentially in the peri-infarct zone.

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 ± 0.08 m/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.

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.