Nitinol Stent Oversizing in Patients Undergoing Popliteal Artery Revascularization: A Finite Element Study

Nitinol stent oversizing is frequently performed in peripheral arteries to ensure a desirable lumen gain. However, the clinical effect of mis-sizing remains controversial. The goal of this study was to provide a better understanding of the structural and hemodynamic effects of Nitinol stent oversizing. Five patient-specific numerical models of non-calcified popliteal arteries were developed to simulate the deployment of Nitinol stents with oversizing ratios ranging from 1.1 to 1.8. In addition to arterial biomechanics, computational fluid dynamics methods were adopted to simulate the physiological blood flow inside the stented arteries. Results showed that stent oversizing led to a limited increase in the acute lumen gain, albeit at the cost of a significant increase in arterial wall stresses. Furthermore, localized areas affected by low Wall Shear Stress increased with higher oversizing ratios. Stents were also negatively impacted by the procedure as their fatigue safety factors gradually decreased with oversizing. These adverse effects to both the artery walls and stents may create circumstances for restenosis. Although the ideal oversizing ratio is stent-specific, this study showed that Nitinol stent oversizing has a very small impact on the immediate lumen gain, which contradicts the clinical motivations of the procedure.Swiss National Science FoundationResearch Council of the Kantonsspital AarauSwiss Heart FoundationGotthard Schettler Foundatio

Chirurgische und interventionelle Behandlung der chronisch-kritischen Beinischämie

Die chronisch-kritische Beinischämie (CLI) ist die schwerste Form der peripher-arteriellen Verschlusskrankheit und geht mit einem erhöhten Risiko für letale kardiovaskuläre Ereignisse einher. Die meisten Patienten überleben aber die ersten Jahre nach Diagnosestellung und sind für den Erhalt ihrer Selbständigkeit auf eine nachhaltige Verbesserung der Beindurchblutung angewiesen. Dieser CME-Artikel fasst die chirurgischen und endovaskulären Optionen zur Revaskularisierung zusammen und geht auf deren Nachhaltigkeit bei CLI ein. Grenzen der verfügbaren Evidenz werden aufgezeigt. Sie beruhen vor allem auf dem Fehlen einer einheitlichen Definition des Behandlungserfolges. Ein klinisch orientierter Lösungsvorschlag wird diskutiert, der helfen könnte, die verschiedenen Behandlungsindikationen zu schärfen. Da sich aber nur die wenigsten Patienten gleich gut für verschiedene Verfahren eignen, werden CLI-Patienten auch in Zukunft am besten in einem interdisziplinär arbeitenden Team betreut sein.Chronic critical limb ischemia (CLI) represents the most severe form of peripheral arterial occlusive disease and is associated with an increased risk for fatal cardiovascular events. However, most patients survive the first years after diagnosis and, to remain independent, depend on durable improvement of limb perfusion. This CME article summarizes the various surgical and endovascular options of revascularization in the context of CLI and discusses their durability. Available evidence is limited which is mainly due to a lack of a generally accepted outcome definition of clinical treatment success. A recently proposed clinically driven measure of success is discussed and how its use could improve definition of specific indications. As only few patients are clinically equally suitable for various treatment options, CLI patients will certainly remain to be managed best within interdisciplinary teams with close collaboration between surgeons and interventionalists

The Importance of Patency in Patients with Critical Limb Ischemia Undergoing Endovascular Revascularization for Infrapopliteal Arterial Disease.

Critical limb ischemia (CLI) represents the most severe form of peripheral arterial disease (PAD) and frequently occurs in medically frail patients. CLI patients frequently exhibit multi-segmental PAD commonly including the tibial arterial segment. Endovascular therapy has been established as first-line revascularization strategy for most CLI patients. Restenosis was reported to occur in up to more than two-thirds of CLI patients undergoing angioplasty of complex tibial arterial obstructions. Nevertheless, favorable clinical outcomes were observed for infrapopliteal angioplasty when compared with bypass surgery, despite higher patency rates for the latter. Based on these observations, infrapopliteal patency was considered to be only of secondary importance upon clinical outcomes in CLI patients. In contrast to these earlier observations, however, recent findings from two randomized clinical trials indicate that infrapopliteal patency does impact on clinical outcomes in CLI patients. The purpose of the present manuscript is to provide a critical reappraisal of the present literature on the clinical importance of tibial arterial patency in CLI patients undergoing endovascular revascularization and to discuss utility and limitations of currently available anti-restenosis technologies

Oversizing and Restenosis with Self-Expanding Stents in Iliofemoral Arteries

Purpose: Uncoated self-expanding nitinol stents (NS) are commonly oversized in peripheral arteries. In current practice, 1-mm oversizing is recommended. Yet, oversizing of NS may be associated with increased restenosis. To provide further evidence, NS were implanted in porcine iliofemoral arteries with a stent-to-artery-ratio between 1.0 and 2.3. Besides conventional uncoated NS, a novel self-expanding NS with an antiproliferative titanium-nitride-oxide (TiNOX) coating was tested for safety and efficacy. Methods: Ten uncoated NS and six TiNOX-coated NS (5-6mm) were implanted randomly in the iliofemoral artery of six mini-pigs. After implantation, quantitative angiography (QA) was performed for calculation of artery and minimal luminal diameter. Follow-up was performed by QA and histomorphometry after 5months. Results: Stent migration, stent fracture, or thrombus formation were not observed. All stents were patent at follow-up. Based on the location of the stent (iliac/femoral) and the stent-to-artery-ratio, stent segments were divided into "normal-sized” (stent-to-artery-ratio<1.4, n=12) and "oversized” (stent-to-artery-ratio≥1.4, n=9). All stent segments expanded to their near nominal diameter during follow-up. Normal-sized stent segments increased their diameter by 6% and oversized segments by 29%. A significant correlation between oversizing and restenosis by both angiography and histomorphometry was observed. Restenosis rates were similar for uncoated NS and TiNOX-coated NS. Conclusions: TiNOX-coated NS are as safe and effective as uncoated NS in the porcine iliofemoral artery. All stents further expand to near their nominal diameter during follow-up. Oversizing is linearly and positively correlated with neointimal proliferation and restenosis, which may not be reduced by TiNOX-coatin

Towards a better understanding of the posttreatment hemodynamic behaviors in femoropopliteal arteries through personalized computational models based on OCT images.

The hemodynamic behavior following endovascular treatment of patients with peripheral arterial disease plays a significant role on the occurrence of restenosis in femoro-popliteal (FP) arteries. The atheroprone flow conditions that are generally accepted to promote restenosis can be calculated by computational fluid dynamics (CFD) analyses, and these results can be used to assess individualized treatment outcomes. However, the impact of endovascular therapy on the flow behaviors of FP arteries are still poorly understood, as the imaging modalities used in existing numerical works (X-ray angiography, computed tomography angiography) are unable to accurately represent the post-treatment arterial geometry due to their low resolutions. Therefore, this study proposes a new algorithm that combines intra-arterial lumen geometry obtained from high-resolution optical coherence tomography (OCT) images with centerlines generated from X-ray images to reconstruct the FP artery with an in-plane resolution of 10 µm. This superior accuracy allows modeling characteristic geometrical structures, such as angioplasty-induced arterial dissections, that are too small to be reconstructed with other imaging modalities. The framework is applied on the clinical data of patients treated either with only-percutaneous transluminal angioplasty (PTA) (n = 4) or PTA followed by stenting (n = 4). Based on the generated models, PTA was found to cause numerous arterial dissections, covering approximately 10% of the total surface area of the lumen, whereas no dissections were identified in the stented arteries. CFD simulations were performed to investigate the hemodynamic conditions before and after treatment. Regardless of the treatment method, the areas affected by low time-averaged wall shear stress (< 0.5 Pa) were significantly higher (p < 0.05) following endovascular therapy (pre-PTA: 0.95 ± 0.59 cm2; post-PTA: 2.10 ± 1.09cm2; post-stent: 3.10 ± 0.98 cm2). There were no statistical differences between the PTA and the stent groups. However, within the PTA group, adverse hemodynamics were mainly concentrated at regions created by arterial dissections, which may negatively impact the outcomes of a leave-nothing-behind strategy. These observations show that OCT-based numerical models have great potential to guide clinicians regarding the optimal treatment approach

Novel Cell-Free Strategy for Therapeutic Angiogenesis: In Vitro Generated Conditioned Medium Can Replace Progenitor Cell Transplantation

BACKGROUND: Current evidence suggests that endothelial progenitor cells (EPC) contribute to ischemic tissue repair by both secretion of paracrine factors and incorporation into developing vessels. We tested the hypothesis that cell-free administration of paracrine factors secreted by cultured EPC may achieve an angiogenic effect equivalent to cell therapy. METHODOLOGY/PRINCIPAL FINDINGS: EPC-derived conditioned medium (EPC-CM) was obtained from culture expanded EPC subjected to 72 hours of hypoxia. In vitro, EPC-CM significantly inhibited apoptosis of mature endothelial cells and promoted angiogenesis in a rat aortic ring assay. The therapeutic potential of EPC-CM as compared to EPC transplantation was evaluated in a rat model of chronic hindlimb ischemia. Serial intramuscular injections of EPC-CM and EPC both significantly increased hindlimb blood flow assessed by laser Doppler (81.2+/-2.9% and 83.7+/-3.0% vs. 53.5+/-2.4% of normal, P<0.01) and improved muscle performance. A significantly increased capillary density (1.62+/-0.03 and 1.68+/-0.05/muscle fiber, P<0.05), enhanced vascular maturation (8.6+/-0.3 and 8.1+/-0.4/HPF, P<0.05) and muscle viability corroborated the findings of improved hindlimb perfusion and muscle function. Furthermore, EPC-CM transplantation stimulated the mobilization of bone marrow (BM)-derived EPC compared to control (678.7+/-44.1 vs. 340.0+/-29.1 CD34(+)/CD45(-) cells/1x10(5) mononuclear cells, P<0.05) and their recruitment to the ischemic muscles (5.9+/-0.7 vs. 2.6+/-0.4 CD34(+) cells/HPF, P<0.001) 3 days after the last injection. CONCLUSIONS/SIGNIFICANCE: Intramuscular injection of EPC-CM is as effective as cell transplantation for promoting tissue revascularization and functional recovery. Owing to the technical and practical limitations of cell therapy, cell free conditioned media may represent a potent alternative for therapeutic angiogenesis in ischemic cardiovascular diseases