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Background: For transcoronary progenitor cells' administration, injections under flow arrest (over-the-wire balloon technique, OTW) are used universally despite lack of evidence for being required for cell delivery or being effective in stimulating myocardial engraftment. Flow-mediated endothelial rolling is mandatory for subsequent cell adhesion and extravasation.Methods: To optimize cell directing toward the coronary endothelium under maintained flow, the authors developed a cell-delivery side-holed perfusion catheter (PC). Thirty-four patients (36-69 years, 30 men) with primary stent-assisted angioplasty-treated anterior MI (peak TnI 151 [53-356]ng/dL, mean[range]) were randomly assigned to OTW or PC autologous ⁹⁹Tc-extametazime-labeled bone marrow CD34(+) cells (4.34 [0.92-7.54] × 10⁶) administration at 6-14 days after pPCI (LVEF 37.1 [24-44]%). Myocardial perfusion (⁹⁹(m)Tc-MIBI) and labeled cells' activity were evaluated (SPECT) at, respectively, 36-48 h prior to and 60 min after delivery.Results: In contrast to OTW coronary occlusions, no intolerance or ventricular arrhythmia occurred with PC cells' administration (P < .001). One hour after delivery, 4.86 [1.7-7.6]% and 5.05 [2.2-9.9]% activity was detected in the myocardium (OTW and PC, respectively, P = .84). Labeled cell activity was clearly limited to the (viable) peri-infarct zone in 88% patients, indicating that the infarct core zone may be largely inaccessible to transcoronary-administered cells.Conclusions: Irrespective of the transcoronary delivery method, only ≈ 5% of native (i.e., non-engineered) CD34(+) cells spontaneously home to the injured myocardium, and cell retention occurs preferentially in the viable peri-infarct zone. Although the efficacy of cell delivery is not increased with the perfusion method, by avoiding provoking ischemic episodes PC offers a rational alternative to the OTW delivery. [ABSTRACT FROM AUTHOR]

PURPOSE: To develop and prospectively evaluate the safety and efficacy of an algorithm for tailoring neuroprotection devices (NPD) and stent types to the patient/lesion in carotid artery stenting (CAS). METHODS: From November 2002 to October 2007, 499 patients (360 men; mean age 65.2+/-8.4 years, range 36-88) were prospectively enrolled in a safety and efficacy study of tailored CAS using proximal (flow blockade or reversal) or distal (filters or occlusion) NPDs and closed- or open-cell self-expanding stents. Of the 535 lesions treated in the study, 175 (32.7%) were 'high risk' by morphology. Half (50.1%) the patients were symptomatic. RESULTS: A quarter (137, 25.6%) of the procedures were performed under proximal protection and the remainder (398, 74.4%) with distal NPDs; the direct stenting rate was 66.9%. High-risk lesions were treated predominantly with a proximal NPD and closed-cell stent (77.1% and 82.9%, respectively) and less frequently by direct stenting (37.1%, p<0.0001 versus non-high-risk lesions). The in-hospital death/stroke rate was 2.0% (95% CI 0.85% to 3.23%), and the death/major stroke rate was 0.7% (95% CI 0.02% to 1.48%). There were no myocardial infarctions, but there was 1 (0.2%) further death within 30 days. With the tailored approach, symptom status and high-risk lesion morphology were not risk factors for an adverse outcome after CAS; only age >75 years (p<0.001) was a predictor of short-term death. Long-term survival (95.4% at 1 and 88.3% at 5 years) was similar for symptomatic versus asymptomatic patients, direct stenting versus predilation, and closed- vs. open-cell stent design; only coronary artery disease adversely impacted survival (p = 0.04). The rates of freedom from death/ipsilateral stroke were 94.9% at 1 year and 85.9% at 5 years. CONCLUSION: Tailored CAS is associated with a low complication rate and high long-term efficacy. CAS operators should have a practical knowledge of different NPDs, including at least one proximal type. [ABSTRACT FROM AUTHOR]

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]