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Towards the Characterisation of Carotid Plaque Tissue Toughness: Linking Mechanical Properties to Plaque Composition
Abstract
Statement of significance:
Calcification plays a fundamental role in plaque tissue mechanics and demonstrates a diverse range of material moduli properties. This work addresses the characterisation of the toughness properties in human carotid plaque tissue using a fracture mechanics approach. Toughness determines the energy required to propagate a controlled cut in the plaque material. This parameter is crucial for predicting the cutting forces required during endovascular cutting balloon angioplasty intervention. Results demonstrate that a strong relationship exists between the structural calcification configurations, fracture mechanisms and associated toughness properties that are characteristic of specific regions within the carotid artery plaque. The identification of the morphological characteristics of localised calcification may serve as a valuable quantitative measure for cutting balloon angioplasty treatment.
... Earlier clinical studies based on coronary computed tomography angiography studies show that coronary calcium artery score was positively associated with plaque progression and future CAD events [26]. However, more recent studies have demonstrated that calcified tissue is very stiff, like rocks, which is not easy to rupture [27]. This would protect the plaque from rupture, rendering it be more stable. ...
Background
A method using in vivo Cine IVUS and VH-IVUS data has been proposed to quantify material properties of coronary plaques. However, correlations between plaque morphological characteristics and mechanical properties have not been studied in vivo.
Method: In vivo Cine IVUS and VH-IVUS data were acquired at 32 plaque cross-sections from 19 patients. Six morphological factors were extracted for each plaque. These samples were categorized into healthy vessel, fibrous plaque, lipid-rich plaque and calcified plaque for comparisons. Three-dimensional thin-slice models were constructed using VH-IVUS data to quantify in vivo plaque material properties following a finite element updating approach by matching Cine IVUS data. Effective Young's moduli were calculated to represent plaque stiffness for easy comparison. Spearman's rank correlation analysis was performed to identify correlations between plaque stiffness and morphological factor. Kruskal-Wallis test with Bonferroni correction was used to determine whether significant differences in plaque stiffness exist among four plaque groups.
Result: Our results show that lumen circumference change has a significantly negative correlation with plaque stiffness (r = −0.7807, p = 0.0001). Plaque burden and calcification percent also had significant positive correlations with plaque stiffness (r = 0.5105, p < 0.0272 and r = 0.5312, p < 0.0193) respectively. Among the four categorized groups, calcified plaques had highest stiffness while healthy segments had the lowest.
Conclusion: There is a close link between plaque morphological characteristics and mechanical properties in vivo. Plaque stiffness tends to be higher as coronary atherosclerosis advances, indicating the potential to assess plaque mechanical properties in vivo based on plaque compositions.
... Similarly, ossified mineral deposits, with their fibrous components, have a greater strength than amorphous mineral. Direct mechanical tests of calcific human atherosclerotic lesions showed that toughness of the plaque segments is substantially greater in locations where the mineral has undergone osteoid metaplasia [173,174]. ...
Vascular calcification, once considered a degenerative, end-stage, and inevitable condition, is now recognized as a complex process regulated in a manner similar to skeletal bone at the molecular and cellular levels. Since the initial discovery of bone morphogenetic protein in calcified human atherosclerotic lesions, decades of research have now led to the recognition that the regulatory mechanisms and the biomolecules that control cardiovascular calcification overlap with those controlling skeletal mineralization. In this review, we focus on key biomolecules driving the ectopic calcification in the circulation and their regulation by metabolic, hormonal, and inflammatory stimuli. Although calcium deposits in the vessel wall introduce rupture stress at their edges facing applied tensile stress, they simultaneously reduce rupture stress at the orthogonal edges, leaving the net risk of plaque rupture and consequent cardiac events depending on local material strength. A clinically important consequence of the shared mechanisms between the vascular and bone tissues is that therapeutic agents designed to inhibit vascular calcification may adversely affect skeletal mineralization and vice versa. Thus, it is essential to consider both systems when developing therapeutic strategies.
... Biomechanical properties of the atherosclerotic plaque tissue are among the critical inputs for accurate numerical simulations and clinical applicability. Several studies have identified the mechanical behavior of peripheral plaque tissue using tensile tests, compressive tests and fracture toughness tests under static loads (Holzapfel et al., 2004;Barrett et al., 2009Barrett et al., , 2016bEbenstein et al., 2009;Maher et al., 2009;Lawlor et al., 2011;Chai et al., 2013;Teng et al., 2014;Cunnane et al., 2015Cunnane et al., , 2016a. Under the fatigue environment of the cardiovascular system, carotid arteries undergo large deformations due to pulsatile blood flow that can often cause atherosclerotic plaque rupture (Bank et al., 2000;Pei et al., 2013;Paritala et al., 2018). ...
Atherosclerotic plaque rupture is a catastrophic event that contributes to mortality and long-term disability. A better understanding of the plaque mechanical behavior is essential for the identification of vulnerable plaques pre-rupture. Plaque is subjected to a natural dynamic mechanical environment under hemodynamic loading. Therefore, it is important to understand the mechanical response of plaque tissue under cyclic loading conditions. Moreover, experimental data of such mechanical properties are fundamental for more clinically relevant biomechanical modeling and numerical simulations for risk stratification. This study aims to experimentally and numerically characterize the stress-relaxation and cyclic mechanical behavior of carotid plaque tissue. Instron microtester equipped with a custom-developed setup was used for the experiments. Carotid plaque samples excised at endarterectomy were subjected to uniaxial tensile, stress-relaxation, and cyclic loading protocols. Thirty percent of the underlying load level obtained from the uniaxial tensile test results was used to determine the change in mechanical properties of the tissue over time under a controlled testing environment (Control tests). The stress-relaxation test data was used to calibrate the hyperelastic (neo-Hookean, Ogden, Yeoh) and linear viscoelastic (Prony series) material parameters. The normalized relaxation force increased initially and slowly stabilized toward the end of relaxation phase, highlighting the viscoelastic behavior. During the cyclic tests, there was a decrease in the peak force as a function of the cycle number indicating mechanical distension due to repeated loading that varied with different frequencies. The material also accumulated residual deformation, which increased with the cycle number. This trend showed softening behavior of the samples. The results of this preliminary study provide an enhanced understanding of in vivo stress-relaxation and cyclic behavior of the human atherosclerotic plaque tissue.
Statement of significance:
This study addresses a gap in current knowledge regarding the influence of plaque location, composition and morphology on the toughness of human femoral plaque tissue. Such information is of great importance to the continued improvement of endovascular treatments, particularly cutting balloon angioplasty (CBA), which require experimentally derived data as a framework for assessing clinical cases and advancing medical devices. This study identifies that femoral plaque tissue exhibits large inter and intra patient and location variance regarding tissue toughness. Increasing calcified plaque content is demonstrated to correlate significantly with increasing toughness. This highlights the potential for predicting target lesion toughness which may lead to an increased adoption of the CBA technique and also further the uptake of endovascular treatment.
Due to the limited number of experimental studies that mechanically characterise human atherosclerotic plaque tissue from the femoral arteries, a recent trend has emerged in current literature whereby one set of material data based on aortic plaque tissue is employed to numerically represent diseased femoral artery tissue. This study aims to generate novel vessel-appropriate material models for femoral plaque tissue and assess the influence of using material models based on experimental data generated from aortic plaque testing to represent diseased femoral arterial tissue.
Novel material models based on experimental data generated from testing of atherosclerotic femoral artery tissue are developed and a computational analysis of the revascularisation of a quarter model idealised diseased femoral artery from a 90% diameter stenosis to a 10% diameter stenosis is performed using these novel material models. The simulation is also performed using material models based on experimental data obtained from aortic plaque testing in order to examine the effect of employing vessel appropriate material models versus those currently employed in literature to represent femoral plaque tissue.
Simulations that employ material models based on atherosclerotic aortic tissue exhibit much higher maximum principal stresses within the plaque than simulations that employ material models based on atherosclerotic femoral tissue. Specifically, employing a material model based on calcified aortic tissue, instead of one based on heavily calcified femoral tissue, to represent diseased femoral arterial vessels results in a 487 fold increase in maximum principal stress within the plaque at a depth of 0.8 mm from the lumen.
Large differences are induced on numerical results as a consequence of employing material models based on aortic plaque, in place of material models based on femoral plaque, to represent a diseased femoral vessel. Due to these large discrepancies, future studies should seek to employ vessel-appropriate material models to simulate the response of diseased femoral tissue in order to obtain the most accurate numerical results.
Background
The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials.Methods
In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up.ResultsCarotid stenosis longer than 0·65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2·79 (1·17–6·65), P = 0·02] and carotid endarterectomy [2·43 (1·03–5·73), P = 0·04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1·68 (1·12–2·53), P = 0·01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0·003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface.Conclusions
Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials.
An anisotropic mechanical behaviour of cortical bone and its intrinsic hierarchical microstructure act as protective mechanisms to prevent catastrophic failure due to natural loading conditions; however, they increase the extent of complexity of a penetration process in the case of orthopaedic surgery. Experimental results available in literature provide only limited information about processes in the vicinity of a tool-bone interaction zone. Also, available numerical models the bone-cutting process do not account for material anisotropy or the effect of damage mechanisms. In this study, both experimental and numerical studies were conducted to address these issues and to elucidate the effect of anisotropic mechanical behaviour of cortical bone tissue on penetration of a sharp cutting tool. First, a set of tool-penetration experiments was performed in directions parallel and perpendicular to bone axis. Also, these experiments included bone samples cut from four different cortices to evaluate the effect of spatial variability and material anisotropy on the penetration processes. Distinct deformation and damage mechanisms linked to different microstructure orientations were captured using a micro-lens high-speed camera. Then, a novel hybrid FE model employing a smoothed-particle-hydrodynamic domain embedded into a continuum FE one was developed based on the experimental configuration to characterise the anisotropic deformation and damage behaviour of cortical bone under a penetration process. The results of our study revealed a clear anisotropic material behaviour of the studied cortical bone tissue and the influence of the underlying microstructure. The proposed FE model reflected adequately the experimental results and demonstrated the need for the use of the anisotropic and damage material model to analyse cutting of the cortical-bone tissue.
We aimed to investigate the effectiveness of a scoring balloon catheter in expanding a circumferentially calcified lesion compared to a conventional balloon catheter using an in vitro experiment setting and elucidate the underlying mechanisms of this ability using a finite element analysis. True efficacy of the scoring device and the underlying mechanisms for heavily calcified coronary lesions are unclear. We employed a Scoreflex scoring balloon catheter (OrbusNeich, Hong Kong, China). The ability of Scoreflex to dilate a calcified lesion was compared with a conventional balloon catheter using 3 different sized calcium tubes. The thickness of the calcium tubes were 2.0, 2.25, and 2.5 mm. The primary endpoints were the successful induction of cracks in the calcium tubes and the inflation pressures required for inducing cracks. The inflation pressure required for cracking the calcium tubes were consistently lower with Scoreflex (p < 0.05, Student t test). The finite element analysis revealed that the first principal stress applied to the calcified plaque was higher by at least threefold when applying the balloon catheter with scoring elements. A scoring balloon catheter can expand a calcified lesion with lower pressure than that of a conventional balloon. The finite element analysis revealed that the concentration of the stress observed in the outside of the calcified plaque just opposite to the scoring element is the underlying mechanism of the increased ability of Scoreflex to dilate the calcified lesion.
This study assesses the suitability of developing a material for use in an experimental model of the carotid baroreceptors. Such a model could then be used in future studies to assess the impact of carotid artery stenting on hemodynamic stability. The material must exhibit a significant measurable electrical response to strain in a fashion analogous to baroreceptor behaviour. A modified electrically conductive silicone (ECS) was examined for use as the material, which was generated from a combination of Wacker LR 3162 and silicone thinner. Samples of the ECS were subjected to uniaxial tensile testing and electrical stimulation in order to mechanically and electrically characterise the material. Testing revealed that the ECS exhibits mechanical behaviour comparable to published data on carotid arterial tissue up to 20% strain and a measurable electrical response to strain in a fashion qualitatively comparable to baroreceptor behaviour. These findings highlight the potential of this material for employment as an experimental model of the carotid baroreceptors.
A study is presented on the relative wear rates of two carbon steels, a Damascus steel and a stainless steel, using the Cutlery and Allied Trades Research Association (CATRA) of Sheffield England cutting test machine. The carbon steels and stainless steel were heat treated to produce a fine array of carbides in a martensite matrix. Tests were done at hardness values of HRC = 41 and 61. At HRC = 61 the stainless steel had slightly superior cutting performance over the carbon steels, while at HRC = 41 the Damascus steel had slightly superior cutting performance.
Carotid artery dissections can be triggered by several factors. The underlying biomechanical phenomena and properties are unclear. This study investigates the dissection properties of 62 human carotid bifurcations using two experimental methods: direct tension and peeling tests. Direct tension tests study the mechanical strength of the tissue components in radial direction, while peeling tests quantify the fracture energy required to propagate a dissection in a tissue. Results show that the interface between the healthy adventitia and media has the highest radial failure stress (132 ± 20 kPa, mean ± SD, n = 25), whereas the lowest value occurs between the diseased intima and media (104 ± 24 kPa, n = 18). The radial tissue strength at the bifurcation is the highest compared with locations that are away from the central region of the bifurcation. Force/width values required to separate the individual layers and to dissect the media in the circumferential direction are always lower than related values in the axial direction, suggesting anisotropic dissection properties. Dissection energies per reference area generated during the peeling tests are also lower for strips in the circumferential direction than for axial strips, and they vary significantly with the location, as shown for the media. Histological investigations demonstrate that interfacial ruptures mainly occur in the media in both types of tests and are 2-5 elastic lamellae away from the external and internal elastic laminae. A remarkably "rougher" dissection surface is generated during axial peeling tests when compared with tests performed in the circumferential direction.
The purpose of this study was to test the hypothesis that mineral maturity and crystallinity index are two different characteristics of bone mineral. To this end, Fourier transform infrared microspectroscopy (FTIRM) was used. To test our hypothesis, synthetic apatites and human bone samples were used for the validation of the two parameters using FTIRM. Iliac crest samples from seven human controls and two with skeletal fluorosis were analyzed at the bone structural unit (BSU) level by FTIRM on sections 2-4 mum thick. Mineral maturity and crystallinity index were highly correlated in synthetic apatites but poorly correlated in normal human bone. In skeletal fluorosis, crystallinity index was increased and maturity decreased, supporting the fact of separate measurement of these two parameters. Moreover, results obtained in fluorosis suggested that mineral characteristics can be modified independently of bone remodeling. In conclusion, mineral maturity and crystallinity index are two different parameters measured separately by FTIRM and offering new perspectives to assess bone mineral traits in osteoporosis.
Purpose
To report a prospective feasibility study of Cutting Balloon angioplasty (CBA) applied in the predilation phase of carotid artery stenting (CAS) in highly calcified lesions.
Methods
From January 2003 to February 2007, 178 consecutive patients (109 men; mean age 73.1±7.3 years) with highly calcified carotid lesions underwent CAS with CBA applied as a pre-specified strategy in the predilation phase of the procedure. All steps in the procedure were performed under cerebral filter protection. The cutting balloon ranged in diameter from 3 to 4 mm and was inflated at nominal pressures in the target lesion. Pre-CBA dilation with a low-profile coronary balloon was performed only when the Cutting Balloon was not able to cross the lesion. Selection of the filters and stents was at the operator's discretion. Primary endpoints were the all stroke and death rates at 30 days and 6 months. Secondary endpoints included Cutting Balloon success (positioning and full balloon inflation), CAS technical success (residual angiographic stenosis <30%), CAS procedural success (technical success and no complications), and in-hospital major complications.
Results
Cutting Balloon success was achieved in all 178 patients. In 32 (18.0%), pre-CBA dilation was necessary due to inability to cross the lesion with the Cutting Balloon initially. CAS technical success was achieved in all patients. One (0.6%) patient suffered transient neurological intolerance due to flow cessation from massive debris in the distal filter; this event was completely resolved after the filter was removed (CAS procedural success 99.4%). One patient suffered a major stroke at day 15 (0.6% 30-day all stroke and death rate). At the 6-month follow-up, 174 (97.7%) patients were evaluated; 1 patient died from myocardial infarction at day 35, and 2 patients died from non-neurological or cardiac causes at days 103 and 158. The cumulative all stroke and death rate was 2.2%.
Conclusion
These data suggest that CBA performed during the predilation phase of CAS in highly calcified lesion is a safe and useful method to prepare this lesion subset for stenting.
Balloon angioplasty typically injures the vessel wall by inducing irregular intimai tears, splits and stretches.1 Proliferative response to this injury,2 and elastic recoil3 after balloon angioplasty are implicated as causes of restenosis and acute closure, respectively. We hypothesized that sharp and regular endovascular surgical incisions may enhance the success of angioplasty by limiting both injury and elastic recoil. We designed devices to make radially directed, longitudinal surgical cuts from the luminal surface deepening into the medial layer. In this study we used 1 of the possible designs (Figure 1). One to 4 cutting edges of 0.1 to 0.4 mm metal blades were mounted on the surface of balloon catheters parallel with the longitudinal axis of the balloon (cutting balloon). The aims of the study were to (1) determine the immediate morphology of incisions made with the cutting balloon; (2) determine the healing response to the endovascular incisions; and (3) compare angiographie results obtained with standard and cutting balloons.
We previously reported that, in a randomized trial, carotid stenting with the use of an emboli-protection device is not inferior to carotid endarterectomy for the treatment of carotid artery disease at 30 days and at 1 year. We now report the 3-year results.
The trial evaluated carotid artery stenting with the use of an emboli-protection device as compared with endarterectomy in 334 patients at increased risk for complications from endarterectomy who had either a symptomatic carotid artery stenosis of at least 50% of the luminal diameter or an asymptomatic stenosis of at least 80%. The prespecified major secondary end point at 3 years was a composite of death, stroke, or myocardial infarction within 30 days after the procedure or death or ipsilateral stroke between 31 days and 1080 days (3 years).
At 3 years, data were available for 260 patients (77.8%), including 85.6% of patients in the stenting group and 70.1% of those in the endarterectomy group. The prespecified major secondary end point occurred in 41 patients in the stenting group (cumulative incidence, 24.6%; Kaplan-Meier estimate, 26.2%) and 45 patients in the endarterectomy group (cumulative incidence, 26.9%; Kaplan-Meier estimate, 30.3%) (absolute difference in cumulative incidence for the stenting group, -2.3%; 95% confidence interval, -11.8 to 7.0). There were 15 strokes in each of the two groups, of which 11 in the stenting group and 9 in the endarterectomy group were ipsilateral.
In our trial of patients with severe carotid artery stenosis and increased surgical risk, no significant difference could be shown in long-term outcomes between patients who underwent carotid artery stenting with an emboli-protection device and those who underwent endarterectomy. (ClinicalTrials.gov number, NCT00231270 [ClinicalTrials.gov].).
In this paper we prove the dry version of the Ten Martini problem: Cantor spectrum with all gaps open, for the extended Harper’s model in the non-self-dual region for Diophantine frequencies.
Background. Severe calcification of the carotid artery has been reported as a contraindication to stenting because the calcium prevents complete expansion of the stent. Cutting balloon angioplasty (CBA) may facilitate carotid stenting of severely calcified lesions by altering plaque morphology. We report the first case series of using CBA to facilitate stenting of heavily calcified carotid arteries. Methods. From August 2004 December 2005, 178 patients underwent carotid artery stenting at Baptist Medical Center-Princeton in Birmingham, Alabama. Of these patients, 23 (13%) had heavily calcified arteries, as determined by angiography and form the basis of this report. Mean patient age was 75 ± 18 yrs and 70% were asymptomatic. All patients were high risk for carotid endarterectomy (CEA). Cerebral protection was used in all but one patient (96%), where severe tortuosity precluded delivery of the protection catheter. Results. Quantitative angiographic analysis revealed baseline stenosis of 86 ± 6%. Following pre-dilatation with a cutting balloon, approximately 1 2 mm less than the reference vessel diameter and subsequent carotid artery stenting, angiographic success was achieved in all lesions with a mean residual post-dilatation stenosis of 14 ± 9%. There were no perioperative neurological complications. One perioperative death occurred secondary to severe hemorrhage from the groin site and anemia associated with ventricular fibrillation. Conclusion. Our series demonstrates the feasibility of stenting heavily calcified carotid arteries with this new pre-dilatation strategy. This study broadens the population of high-risk patients suitable for carotid artery stenting.
Atherosclerosis is a disease that causes obstructions to develop within the arterial system; these obstructions can result in an acute vascular event such as a heart attack or stroke, and potentially death. In the majority of cases a standard angioplasty balloon is sufficient to dilate the site of an obstruction; however difficult obstructions, such as heavily calcified lesions require specialist dilation solutions. One such example of a device is Boston Scientific's cutting balloon. An analysis of the Food and Drug Administration's (FDA) Manufacturer and User Facility Device Experience (MAUDE) database demonstrates that the original cutting balloon has a number of distinct adverse events associated with it. In this study we describe the design, manufacturing, and testing of a new force focused angioplasty balloon that has the potential to reduce or eliminate the adverse events associated with the Boston Scientific cutting balloon. This design incorporates two elastomeric materials to aid recoiling of the device namely: nitinol and a silicone elastomer. New methods of manufacturing are described in this study, that ensure that precision molding and assembly can occur. To determine the effectiveness of our device, we simulated concentric calcified lesions with a surrogate chalk model. These results demonstrate that our device has a significantly lower lesion burst pressure in comparison to a standard angioplasty balloon, 174 atm versus 12.48 atm. To determine if our device reduced potential snagging, and thus reduced the risk of withdrawal resistance being encountered, we performed a withdrawal resistance test. A noticeably lower withdrawal force is associated with our device, the high peaks on the Boston Scientific device indicate that there may be wings forming on the balloon and these are catching on the tip of the introducer sheath. Finally, we demonstrated in vivo efficacy of our device in a porcine model. By the use of elastomeric recoiling features in a new cutting balloon design we have been able to overcome the three main reported adverse events associated with the Boston Scientific cutting balloon. Subsequently we experimentally demonstrated this improved efficacy for one particular peripheral balloon size (e.g., 5 mm diameter).
Vascular calcification is an unfavorable event in the natural history of atherosclerosis that predicts cardiovascular morbidity and mortality. However, increasing evidence suggests that different calcification patterns are associated with different or even opposite histopathological and clinical features, reflecting the dual relationship between inflammation and calcification. In fact, initial calcium deposition in response to pro-inflammatory stimuli results in the formation of spotty or granular calcification ("microcalcification"), which induces further inflammation. This vicious cycle favors plaque rupture, unless an adaptive response prevails, with blunting of inflammation and survival of vascular smooth muscle cells (VSMCs). VSMCs promote fibrosis and also undergo osteogenic transdifferentiation, with formation of homogeneous or sheet-like calcification ("macrocalcification"), that stabilizes the plaque by serving as a barrier towards inflammation. Unfortunately, little is known about the molecular mechanisms regulating this adaptive response. The advanced glycation/lipoxidation endproducts (AGEs/ALEs) have been shown to promote vascular calcification and atherosclerosis. Recent evidence suggests that two AGE/ALE receptors, RAGE and galectin-3, modulate in divergent ways, not only inflammation, but also vascular osteogenesis, by favoring "microcalcification" and "macrocalcification", respectively. Galectin-3 seems essential for VSMC transdifferentiation into osteoblast-like cells via direct modulation of the WNT-β-catenin signaling, thus driving formation of "macrocalcification", whereas RAGE favors deposition of "microcalcification" by promoting and perpetuating inflammation and by counteracting the osteoblastogenic effect of galectin-3. Further studies are required to understand the molecular mechanisms regulating transition from "microcalcification" to "macrocalcification", thus allowing to design therapeutic strategies which favor this adaptive process, in order to limit the adverse effects of established atherosclerotic calcification.
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Coronary artery calcification is a well-established predictor of future cardiac events; however, it is not a predictor of unstable plaque. The intimal calcification of the atherosclerotic plaques may begin with smooth muscle cell apoptosis and release of matrix vesicles and is almost always seen microscopically in pathological intimal thickening, which appears as microcalcification (≥0.5 μm, typically <15 μm in diameter). Calcification increases with macrophage infiltration into the lipid pool in early fibroatheroma where they undergo apoptosis and release matrix vesicles. The confluence of calcified areas involves extracellular matrix and the necrotic core, which can be identified by radiography as speckled (≤2 mm) or fragmented (>2, <5 mm) calcification. The calcification in thin-cap fibroatheromas and plaque rupture is generally less than what is observed in stable plaques and is usually speckled or fragmented. Fragmented calcification spreads into the surrounding collagen-rich matrix forming calcified sheets, the hallmarks of fibrocalcific plaques. The calcified sheets may break into nodules with fibrin deposition, and when accompanied by luminal protrusion, it is associated with thrombosis. Calcification is highest in fibrocalcific plaques followed by healed plaque rupture and is the least in erosion and pathological intimal thickening. The extent of calcification is greater in men than in women especially in the premenopausal period and is also greater in whites compared with blacks. The mechanisms of intimal calcification remain poorly understood in man. Calcification often occurs in the presence of apoptosis of smooth muscle cells and macrophages with matrix vesicles accompanied by expression of osteogenic markers within the vessel wall.
Recent experimental studies performed on human carotid plaques have focused on mechanical characterisation for the purpose of developing material models for finite element analysis without quantifying the tissue composition or relating mechanical behaviour to pre-operative classification. This study characterises the mechanical and biological properties of 25 human carotid plaques as well as investigates the common features that lead to plaque rupture during mechanical testing by performing circumferential uniaxial tests, Fourier Transform Infra-Red (FTIR) and scanning electron microscopy (SEM) on each specimen to relate plaque composition to mechanical behaviour. Mechanical results revealed large variations between plaque specimen behaviour with no correlation to pre-operative ultrasound prediction. However, FTIR classification demonstrated a statistically significant relationship between stress and stretch values at rupture and the level of calcification (p = 0.002 and p = 0.009). Energy dispersive X-ray spectroscopy was carried out to confirm that the calcium levels observed using FTIR analysis were accurate. This work demonstrates the potential of FTIR as an alternative method to ultrasound of predicting plaque mechanical behaviour. SEM imaging at the rupture sites of each specimen highlighted voids created by the nodes of calcifications in the tissue structure which could lead to increased vulnerability of the plaque.
Our bones are full of microscopic cracks, but the hierarchical character of the bones’ structure—from molecular to macroscopic scales—makes them remarkably resistant to fracture.
OBJECTIVES: This study aims to evaluate the rate of stent malapposition, plaque prolapse and fibrous cap rupture detected by optical coherence tomography (OCT) imaging according to carotid stent design. DESIGN: It was a prospective single-centre study. MATERIALS AND METHODS: Forty consecutive patients undergoing protected carotid artery stenting (CAS) and high-definition OCT image acquisition were enrolled in the study. OCT frames were analysed off-line, in a dedicated core laboratory by two independent physicians. Cross-sectional OCT images within the stented segment of the internal carotid artery were evaluated at 1-mm intervals for the presence of strut malapposition, plaque prolapse and fibrous cap rupture according to stent design. RESULTS: Closed-cell design stents (CC) were used in 17 patients (42.5%), open-cell design stents (OC) in 13 (32.5%) and hybrid design stents (Hyb) in 10 (25%). No procedural or post-procedural neurological complications occurred (stroke/death 0% at 30 days). On OCT analysis the frequencies of malapposed struts were higher with CC compared to OC and Hyb (34.5% vs 15% and 16.3%, respectively; p < 0.01). Plaque prolapse was more frequent with OC vs CC (68.6% vs 23.3%; p < 0.01) and vs Hyb stents (30.8%; p < 0.01). Significant differences were also noted in the rates of fibrous cap rupture between CC and OC (24.2% vs 43.8%; p < 0.01), and between CC and Hyb (24.2% vs 39.6%; p < 0.01), but not between OC and Hyb stents (p = 0.4). CONCLUSION: Intravascular OCT after CAS revealed that micro-defects after stent deployment are frequent and are related to the design of implanted stents. Stent malapposition is more frequent with CC stents, while plaque prolapse is more common with OC stents. It remains, however, unknown whether these figures now detected with OCT are of any clinical and prognostic significance.
Background:
Spontaneous rupture of the aorta (SRA) without aneurysm, dissection, inflammation or infection of the aortic wall can be of two types: traumatic and non-traumatic. SRA is most of the time a fatal event. Consequently, it is important to understand the conditions which lead to the aortic rupture, and, in the case of non-traumatic SRA, to predict the temporal likelihood of rupture.
Method of approach:
The present work incorporates the temporal aspect by examining the effects of fatigue on aortic wall properties, and adopts an energy approach, based on fracture toughness, to evaluate the aorta's resistance to rupture. Fracture toughness characterization is a destructive testing process and as a consequence cannot be implemented as a clinical tool. However, using concepts in damage mechanics, in theory, it should be possible to indirectly assess fracture toughness from other mechanical properties, such as aortic wall stiffness. Tissue samples from non-aneurysmal porcine aortas were fatigued and were subjected to both biaxial and guillotine tests to assess wall stiffness variations and fracture toughness exhaustion, respectively.
Results:
The experiments reveal that aortic wall stiffness variations and fracture toughness exhaustion decreased as a function of loading cycles and can be modeled with exponential functions. After one million loading cycles, the stiffness ratio between the non-fatigued sample and the fatigued sample, dropped to about 0.85, while the fracture toughness ratio counterpart fell to about 0.80.
Conclusion:
Consequently, the changes in both stiffness and fracture toughness as a function of applied fatigue cycles can be measured in aortic tissues. Moreover, these results suggest the possibility to use fracture toughness exhaustion curves as a fatigue criterion.
Background:
Endovascular treatment by transluminal balloon angioplasty or stent insertion may be a useful alternative to carotid endarterectomy for the treatment of atherosclerotic carotid artery stenosis. This review updates a previous version first published in 1997 and subsequently updated in 2004 and 2007.
Objectives:
To assess the benefits and risks of endovascular treatment compared with carotid endarterectomy or medical therapy in patients with symptomatic or asymptomatic carotid stenosis.
Search methods:
We searched the Cochrane Stroke Group Trials Register (last searched January 2012) and the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4), MEDLINE (1950 to January 2011), EMBASE (1980 to January 2011) and Science Citation Index (1945 to January 2011). We also searched ongoing trials registers (January 2011) and reference lists and contacted researchers in the field.
Selection criteria:
Randomised trials comparing endovascular treatment (including balloon angioplasty or stenting) with endarterectomy or medical therapy for symptomatic or asymptomatic atherosclerotic carotid stenosis.
Data collection and analysis:
One review author selected trials for inclusion, assessed trial quality and extracted data. A second review author independently validated trial selection and a third review author independently validated data extraction. We calculated treatment effects as odds ratios (OR) and 95% confidence intervals (CI), with endovascular treatment as the reference group. We quantified heterogeneity using the I(2) statistic.
Main results:
We included 16 trials involving 7572 patients. In patients with symptomatic carotid stenosis at standard surgical risk, endovascular treatment was associated with a higher risk of the following outcome measures occurring between randomisation and 30 days after treatment than endarterectomy: death or any stroke (the primary safety outcome) (OR 1.72, 95% CI 1.29 to 2.31, P = 0.0003; I(2) = 27%), death or any stroke or myocardial infarction (OR 1.44, 95% CI 1.15 to 1.80, P = 0.002; I(2) = 7%), and any stroke (OR 1.81, 95% CI 1.40 to 2.34, P < 0.00001;I(2) = 12%). The OR for the primary safety outcome was 1.16 (95% CI 0.80 to 1.67) in patients < 70 years old and 2.20 (95% CI 1.47 to 3.29) in patients ≥ 70 years old (interaction P = 0.02).The rate of death or major or disabling stroke did not differ significantly between treatments (OR 1.28, 95% CI 0.93 to 1.77, P = 0.13; I(2) = 0%). Endovascular treatment was associated with lower risks of myocardial infarction (OR 0.44, 95% CI 0.23 to 0.87, P = 0.02; I(2) = 0%), cranial nerve palsy (OR 0.08, 95% CI 0.05 to 0.14, P < 0.00001; I(2) = 0%) and access site haematomas (OR 0.37, 95% CI 0.18 to 0.77, P = 0.008; I(2) = 27%).The combination of death or any stroke up to 30 days after treatment or ipsilateral stroke during follow-up (the primary combined safety and efficacy outcome) favoured endarterectomy (OR 1.39, 95% CI 1.10 to 1.75, P = 0.005; I(2) = 0%), but the rate of ipsilateral stroke after the peri-procedural period did not differ between treatments (OR 0.93, 95% CI 0.60 to 1.45, P = 0.76; I(2) = 0%).Restenosis during follow-up was more common in patients receiving endovascular treatment than in patients assigned surgery (OR 2.41, 95% CI 1.28 to 4.53, P = 0.007; I(2) = 55%). In patients with asymptomatic carotid stenosis, treatment effects on the primary safety (OR 1.71, 95% CI 0.78 to 3.76, P = 0.18; I(2) = 0%) and combined safety and efficacy outcomes (OR 1.75, 95% CI 0.92 to 3.33, P = 0.09; I(2) = 0%) were similar to symptomatic patients, but differences between treatments were not statistically significant. Among patients not suitable for surgery, the rate of death or any stroke between randomisation and end of follow-up did not differ significantly between endovascular treatment and medical care (OR 0.22, 95% CI 0.01 to 7.92, P = 0.41; I(2)= 79%).
Authors' conclusions:
Endovascular treatment is associated with an increased risk of peri-procedural stroke or death compared with endarterectomy. However, this excess risk appears to be limited to older patients. The longer term efficacy of endovascular treatment and the risk of restenosis are unclear and require further follow-up of existing trials. Further trials are needed to determine the optimal treatment for asymptomatic carotid stenosis.
Thin slices of soft flexible solids have negligible bending resistance and hence store negligible elastic strain energy; furthermore such offcuts are rarely permanently deformed after slicing. Cutting forces thus depend only on work of separation (toughness work) and friction. These simplifying assumptions are not as restrictive as it might seem, and the mechanics are found to apply to a wide variety of foodstuffs and biological materials. The fracture toughness of such materials may be determined from cutting experiments: the use of scissors instrumented for load and displacement is a popular method where toughness is obtained from the work areas beneath load–displacement plots. Surprisingly, there is no analysis for the variation of forces with scissor blade opening and this paper provides the theory. Comparison is made with experimental results in cutting with scissors. The analysis is generalised to cutting with blades of variable curvature and applied to a commercial food cutting device having a rotating spiral plan form blade. The strong influence of the ‘slice/push ratio’ (blade tangential speed to blade edge normal speed) on the cutting forces is revealed. Small cutting forces are important in food cutting machinery as damage to slices is minimised. How high slice/push ratios may be achieved by choice of blade profile is discussed.
The sharpness of a blade is a key parameter in cutting soft solids, such as biological tissues, foodstuffs or elastomeric materials. It has a first order effect on the effort, and hence energy needed to cut, the quality of the cut surface and the life of the cutting instrument. To date, there is no standard definition, measurement or protocol to quantify blade sharpness. This paper derives a quantitative index of blade sharpness via indentation experiments in which elastomeric materials are cut using both sharp and blunt straight edge blades. It is found that the depth of blade indentation required to initiate a cut or crack in the target material is a function of the condition or sharpness of the blade’s cutting edge, and this property is used to formulate a so-called “blade sharpness index” (BSI). It is shown theoretically that this index is zero for an infinitely sharp blade and increases in a quadratic manner for increasing bluntness. For the blades tested herein, the sharpness index was found to vary between 0.2 for sharp blades and 0.5 for blunt blades, respectively. To examine the suitability of the index in other cutting configurations, experiments are performed using different blade types, target materials and cutting rates and it is found that the index is independent of the target material and cutting rate and thus pertains to the blade only. In the companion Part II to this paper a finite element model is developed to examine the effect of blade geometry on the sharpness index derived herein.
The carotid bulb is innervated by the sinus nerve of Hering, a branch of the glossopharyngeal nerve, derived from the third pharyngeal arch. The aim of this study was to determine the frequency, predictors, and outcome of the carotid BR after carotid stent placement according to the location of the plaque lesion.
Atherosclerotic carotid plaques of apical versus body lesions were prospectively analyzed in 95 consecutive patients who underwent carotid stent placement. Patients with hypertension after stent placement were excluded, and transient (<3 hours) and prolonged (3-24 hours) BR, together with AEs such as strokes and death, were assessed in the 2 lesion locations (apical versus body). Other factors known to affect the carotid baroreceptor were also investigated, and the results were analyzed by χ(2) or Mann-Whitney U tests.
Transient BR occurred in 30% of apical lesions in contrast to 70% of body lesions (P = .001). Transient BR showed a significant relationship to lesion location (P = .001), occurring most frequently in body lesions, and to the distance of maximum stenosis from the ICA ostium (P = .001). Hyperperfusion and AE rates (P = .076) in 1 month occurred more frequently in apical lesions.
The frequency of transient BR after carotid stent placement was lower in the apical region of the carotid bulb. Different cardiovascular disturbances after carotid stent placement can be attributed to anatomically different areas of the carotid bulb.
Recent works demonstrated the difference of calcification genesis between carotid and femoral plaques, femoral plaques being more calcified. It has been clearly demonstrated that the molecular triad osteoprotegerin (OPG)/Receptor Activator of NFkB (RANK)/RANK Ligand (RANKL) exerts its activities in the osteoimmunology and vascular system. The aim of this study was to determine their expression and their potential role in calcifications of the atheromatous plaques located in two different peripheral arterial beds, carotid and femoral. The expression of OPG, RANK and RANKL was analyzed by immunochemistry in 40 carotid and femoral samples. Blood OPG and RANKL were quantified using specific ELISA assays. OPG staining was more frequently observed in carotid than in femoral plaques, especially in lipid core. Its expression correlated with macrophage infiltration more abundantly observed in carotid specimens. Surprisingly, serum OPG concentration was significantly lower in carotid population compared to femoral population while RANK and RANKL were equally expressed in both arterial beds. Carotid plaques that are less rich in calcium than femoral specimens, express more frequently OPG, this expression being correlated with the abundance of macrophages in the lesions. These data strengthen the key role played by OPG in the differential calcification in carotid and femoral plaques.
The forces and hence fracture energies required to cut bone are presented in this paper and the merits of cutting with a high speed blade are considered. A plain knife blade was used to cut cancellous and compact lamb bone using three different methods. A microtome was used to produce a range of cut thicknesses which enabled the fracture energy to be separated into friction, surface fracture and plastic deformation energies. A tensile test machine was used to produce thicker off-cuts so that the energy required to cut through full sections of bone could be determined. A high speed rail gun was used to cut at speeds up to 130 m/s. The energy required to cut bone did not change with blade speed. However, the energies measured during the cutting varied over a wide range. In situations in which the surface of the cut bone exhibited a very uneven surface high energy was required, whereas when the resulting cut surface was planar the cutting energy was low. A light weight blade which impacts the bone at high speed will transmit a small impulse to the carcass which may be absorbed without transmitting strain to the muscle/connective tissue. This may allow the development of a high speed knife which will cut bone without excessively damaging the meat surrounding the cut.
Results of endovascular repair vary according to the arterial bed. We hypothesized that these differences may be related to the plaque features. To explore this hypothesis, we designed a prospective study that compared carotid and femoral atheroma.
Patients that underwent femoral or carotid endarterectomy were included in our study. Demographic data and blood sampling were obtained prior to surgery. Plaques were evaluated for AHA grading, calcification and lipid content. Eighty-eight plaques were harvested during this study (45 carotid specimens and 43 femoral specimens). No differences were noted between carotid and femoral groups regarding demographic and biological data. Histological data more frequently showed fibrous cap atheroma in carotid arteries (75%) and fibrocalcific plaques in femoral arteries (93%), p<0.001. Morphological analyses showed a high prevalence of osteoid metaplasia in femoral arteries (63%) compared to carotid arteries (20%, p<0.001). Biochemical analyses were consistent with histological data, showing higher calcium and lesser cholesterol concentrations in femoral than in carotid plaques (p<0.01).
Femoral and carotid plaques showed different morphology in comparable groups of patients.
Calcified coronary lesions may be associated with stent underexpansion, malapposition, and high rates of restenosis. The use of drug-eluting stents (DES) in such lesions has not been fully addressed in the major trials. We sought to examine the outcomes of patients who were treated with plaque modification (PM) to facilitate DES implantation.
We analyzed 164 calcified coronary lesions in 145 consecutive patients who underwent aggressive PM with either rotational atherectomy (RA) and/or cutting balloon (CB) before DES implantation. CB was used in moderate calcified lesions and RA alone or followed by CB in severe calcified lesions.
Patients were 68.7 +/- 10.1 years old, 47% were diabetic, 34% had left ventricular ejection fraction (LVEF) < or =50%, and 39% had 3-vessel disease. Ninety-five percent of lesions were classified as B2/C, 100% as moderately/severely calcified. PM was achieved by using CB in 57% and by RA alone or followed by CB in 43%. In 100%, a DES was implanted. There was no failure to deliver a stent. At 15 +/- 11 months follow-up, the overall major adverse cardiac events (MACE) rate was 9.6% (3.4% cardiac death, 2.3% myocardial infarction, and 3.4% target lesion revascularization [TLR]). The only independent predictor of MACE was LVEF < or =50% (odds ratio 3.88; 95% confidence interval: 1.15-13.1; P = 0.03). The incidence of stent thrombosis (ST) was 2.1%. There were no significant differences in MACE and TLR based on the type of PM used.
In this population at high risk of restenosis, aggressive PM by CB and/or RA before DES implantation provides excellent mid-term outcomes with only 3.4% TLR and 2.1% ST.
Clinical events such as heart attack and stroke can be caused by the rupture of atherosclerotic plaques in artery walls. Computational modeling is often used to better understand atherosclerotic disease progression to identify "vulnerable" plaques (i.e., those likely to rupture) and to tailor treatments according to tissue composition. However, because of the heterogeneity of plaque tissue, there are limited data available on the material properties of individual plaque constituents. The goal of this study was to use nanoindentation to measure the mechanical properties of blood clots, fibrous tissue, partially calcified fibrous tissue, and bulk calcifications from human atherosclerotic plaque tissue. Fourier transform infrared (FTIR) spectroscopy was used to quantify the amount of mineral and lipid in each tissue region tested. The results demonstrate that the stiffness of plaque tissue increases with increasing mineral content. In addition, by providing the first experimental data on atherosclerotic calcifications, these data show that some of the estimated modulus values commonly used in computational models greatly underestimate the stiffness of the fully calcified tissue.
Fluid velocities were measured by laser Doppler velocimetry under conditions of pulsatile flow in a scale model of the human carotid bifurcation. Flow velocity and wall shear stress at five axial and four circumferential positions were compared with intimal plaque thickness at corresponding locations in carotid bifurcations obtained from cadavers. Velocities and wall shear stresses during diastole were similar to those found previously under steady flow conditions, but these quantities oscillated in both magnitude and direction during the systolic phase. At the inner wall of the internal carotid sinus, in the region of the flow divider, wall shear stress was highest (systole = 41 dynes/cm2, diastole = 10 dynes/cm2, mean = 17 dynes/cm2) and remained unidirectional during systole. Intimal thickening in this location was minimal. At the outer wall of the carotid sinus where intimal plaques were thickest, mean shear stress was low (-0.5 dynes/cm2) but the instantaneous shear stress oscillated between -7 and +4 dynes/cm2. Along the side walls of the sinus, intimal plaque thickness was greater than in the region of the flow divider and circumferential oscillations of shear stress were prominent. With all 20 axial and circumferential measurement locations considered, strong correlations were found between intimal thickness and the reciprocal of maximum shear stress (r = 0.90, p less than 0.0005) or the reciprocal of mean shear stress (r = 0.82, p less than 0.001). An index which takes into account oscillations of wall shear also correlated strongly with intimal thickness (r = 0.82, p less than 0.001). When only the inner wall and outer wall positions were taken into account, correlations of lesion thickness with the inverse of maximum wall shear and mean wall shear were 0.94 (p less than 0.001) and 0.95 (p less than 0.001), respectively, and with the oscillatory shear index, 0.93 (p less than 0.001). These studies confirm earlier findings under steady flow conditions that plaques tend to form in areas of low, rather than high, shear stress, but indicate in addition that marked oscillations in the direction of wall shear may enhance atherogenesis.
The distribution of nonstenosing, asymptomatic intimal plaques in 12 adult human carotid bifurcations obtained at autopsy was compared with the distribution of flow streamline patterns, flow velocity profiles, and shear stresses in corresponding scale models. The postmortem specimens were fixed while distended to restore normal in vivo length, diameter, and configuration. Angiograms were used to measure branch angles and diameters, and transverse histological sections were studied at five standard sampling levels. Intimal thickness was determined at 15 degrees intervals around the circumference of the vessel sections from contour tracings of images projected onto a digitizing plate. In the models, laser-Doppler anemometry was used to determine flow velocity profiles and shear stresses at levels corresponding to the standard specimen sampling sites under conditions of steady flow at Reynolds numbers of 400, 800, and 1200, and flow patterns were visualized by hydrogen bubble and dye-washout techniques. Intimal thickening was greatest and consistently eccentric in the carotid sinus. With the center of the flow divider as the 0 degree index point, mid-sinus sections showed minimum intimal thickness (0.05 +/- 0.02 mm) within 15 degrees of the index point, while maximum thickness (0.9 +/- 0.1 mm) occurred at 161 +/- 16 degrees, i.e., on the outer wall opposite the flow divider. Where the intima was thinnest, along the inner wall, flow streamlines in the model remain axially aligned and unidirectional, with velocity maxima shifted toward the flow divider apex. Wall shear stress along the inner wall ranged from 31 to 600 dynes/cm2 depending on the Reynolds number. Where the intima was thickest, along the outer wall opposite the flow divider apex, the pattern of flow was complex and included a region of separation and reversal of axial flow as well as the development of counter-rotating helical trajectories. Wall shear stress along the outer wall ranged from 0 to -6 dynes/cm2. Intimal thickening at the common carotid and distal internal carotid levels of section was minimal and was distributed uniformly about the circumference. We conclude that in the human carotid bifurcation, regions of moderate to high shear stress, where flow remains unidirectional and axially aligned, are relatively spared of intimal thickening. Intimal thickening and atherosclerosis develop largely in regions of relatively low wall shear stress, flow separation, and departure from axially aligned, unidirectional flow. Similar quantitative evaluations of other atherosclerosis-prone locations and corresponding flow profile studies in geometrically accurate models may reveal which of these hemodynamic conditions are most consistently associated with the development of intimal disease.
This paper reviews the progress that has been made in applying the principles of fracture mechanics to the topic of fracture of long bones. Prediction of loading conditions which result in the propagation of fractures in bones has been of interest to the field of trauma biomechanics and orthopedics for over one hundred years. Independent verifications, by various investigators, of bone fracture mechanics parameters are reviewed and investigations of the effects of bone density and specimen thickness on the critical fracture mechanics parameters and of other factors such as critical crack length and plastic zone size in bovine femoral bone, and the effects of crack velocity on fracture mechanics parameters in bovine tibial bone are discussed. It took over ten years for the techniques of bone fracture mechanics to be applied to human compact bone, due primarily to geometric constraints from the smaller size of human bones. That work will be reviewed along with other continuing work to define the orientation dependence of the fracture mechanics parameters in bone and to refine the experimental techniques needed to overcome the geometric constraints of specimen size. A discussion is included of work still needed to determine fracture mechanics parameters for transverse and longitudinal crack propagation in human bone and to establish the effects of age on those parameters. Finally, a discussion will be given of how this knowledge needs to be extended to allow prediction of whole bone fracture from external loading to aid in the design of protective systems.
A 65-year-old man with a restenotic lesion of the mid LAD was scheduled for Wiktor stent placement. The IVUS revealed circumferential severe calcification. Two conventional, non-compliant angioplasty balloons inflated to high pressures failed to achieved sufficient dilatation and both ruptured. At this point, we selected high pressure inflation of the Cutting Balloon. The Cutting Balloon achieved adequate dilation for stenting and proved to be useful in predilating a circumferential, heavily calcified lesion.
Calcium deposits emerge in young people as granules of microscopic size in atherosclerotic lesions defined histologically as type IV. Granules are found among the vast quantity of extracellular lipid droplets and cell remnants that form the core of this lesion type, and intracellularly within smooth muscle cells that have been disrupted and impaired by the accumulated extracellular material. Extracellular calcium granules are, in part, granules that formed intracellularly and were set free through cell death, and in part they represent extracellular calcification of cell remnants. Extracellular granules combine and grow to form large structures until, in adults past the fourth decade of life, the greater part of a lesion core may be calcified (type VII lesion). Organization off calcium deposits into bone (osseous metaplasia) may occur as a late step.
The fate of human lesion components subsequent to therapeutic lowering of high blood cholesterol is not known. In rhesus monkeys, 3½ years off drastic reduction of high blood cholesterol resulted in complete loss of macrophages, macrophage foam cells, and lymphocytes and loss or reduction of extracellular accumulations of lipid and cell remnants from advanced lesions. Calcium deposits, however, remained in the arterial wall and were not visibly changed. Osseous metaplasia of calcium deposits did not occur in monkeys over a 9-year period of lesion progression and regression.
The aim of the study was to evaluate the feasibility, safety, and efficacy of cutting balloon angioplasty in treatment of angiographically moderate and severe calcified coronary lesions. Thirty-seven calcified coronary lesions (29 patients) detected by angiography were dilated with cutting balloon. Predilatation with plain balloon was performed in 27 (73.0%) lesions and stent was implanted in 23 (62.2%) lesions following cutting balloon. Acute gain following cutting balloon in predilated lesions was compared to the acute gain following plain balloon predilatation. For predilated lesions, acute gain after cutting balloon was significantly greater compared with plain balloon predilatation (1.51 +/- 0.49 vs. 0.77 +/- 0.42; P = 0.01). This result was achieved with larger size and lower pressure of cutting balloon compared with plain balloon (3.28 +/- 0.46 vs. 2.94 +/- 0.55, P = 0.01; 10.38 +/- 1.64 vs. 13.19 +/- 3.63, P = 0.001, respectively). The final gain following cutting balloon dilatation was significantly higher than the expected gain obtained by using a plain balloon of the same size (1.51 +/- 0.49 vs. 0.93 +/- 0.48; P < 0.0001), which was inflated at significantly higher pressure compared with cutting balloon. When we compared acute gain following cutting balloon in lesions with and without predilatation, we found no significant difference (P = 0.31). Angiographic success was achieved in 36 (97.3%) lesions and procedural success in 33 (89.1%) lesions. In-hospital major adverse cardiac event (MACE) occurred in three (10.3%) patients. Follow-up MACE was reported from three (10.3%) patients. In conclusion, cutting balloon angioplasty is feasible and safe in treatment of angiographically moderate and severe calcified lesions. Dilating efficiency of cutting balloon seems to be greater compared with a plain balloon of the same size, which was inflated at significantly higher pressure compared with cutting balloon. These results can be achieved with low in-hospital MACE and are associated with a good long-term outcome.
The cutting balloon (CB) is a specialized device designed to create discrete longitudinal incisions in the atherosclerotic target coronary segment during balloon inflation. Such controlled dilatation theoretically reduces the force needed to dilate an obstructive lesion compared with standard percutaneous transluminal coronary angioplasty (PTCA). We report a multicenter, randomized trial comparing the incidence of restenosis after CB angioplasty versus conventional balloon angioplasty in 1,238 patients. Six hundred seventeen patients were randomized to CB treatment, and 621 to PTCA. The mean reference vessel diameter was 2.86 +/- 0.49 mm, mean lesion length 8.9 +/- 4.3 mm, and prevalence of diabetes mellitus in patients was 13%. The primary end point, the 6-month binary angiographic restenosis rate, was 31.4% for CB and 30.4% for PTCA (p = 0.75). Acute procedural success, defined as the attainment of <50% diameter stenosis without in-hospital major adverse cardiac events, was 92.9% for CB and 94.7% for PTCA (p = 0.24). Freedom from target vessel revascularization was slightly higher in the CB arm (88.5% vs 84.6%, log-rank p = 0.04). Five coronary perforations occurred in the CB arm only (0.8% vs 0%, p = 0.03). At 270 days, rates of myocardial infarction, death, and total major adverse cardiac events for CB and PTCA were 4.7% versus 2.4% (p = 0.03), 1.3% versus 0.3% (p = 0.06), and 13.6% versus 15.1% (p = 0.34), respectively. In summary, the proposed mechanism of controlled dilatation did not reduce the rate of angiographic restenosis for the CB compared with conventional balloon angioplasty. CB angioplasty should be reserved for difficult lesions in which controlled dilatation is believed to provide a better acute result compared with balloon angioplasty alone.
Several studies have shown that mechanisms for lumen enlargement following conventional balloon angioplasty (BA) consist of plaque reduction and vessel expansion. To assess the mechanisms of lumen enlargement after Cutting Balloon (CB) angioplasty, intravascular ultrasound images were analyzed in 180 lesions (89 CB and 91 BA). External elastic membrane (EEM) cross-sectional area (CSA), lumen CSA, and plaque plus media (P+M) CSA were measured before and after angioplasty. In the CB group, lower balloon pressure was utilized (P < 0.0001). DeltaP+M CSA was significantly larger (P = 0.02) and deltalumen CSA showed a trend toward being larger (P = 0.07) compared to BA group. For noncalcified lesions, CB resulted in a larger deltaP+M CSA (P < 0.05) and a smaller deltaEEM CSA (P = 0.10) than BA. For calcified lesions, deltalumen CSA was significantly larger in the CB group (P < 0.05) without significant differences in deltaEEM CSA and deltaP+M CSA. Dissections complicated with calcified lesions were associated with larger deltalumen CSA for the CB group. In conclusion, for noncalcified lesions, CB achieves similar luminal dimensions with larger plaque reduction and less vessel expansion compared to BA. On the other hand, for calcified lesions, the CB achieves larger lumen gain, especially in lesions with evidence of dissections.
We report a rare complication due to fracture of the blade of a cutting balloon in the setting of a tough nondilatable restenotic lesion. This resulted in a mural hematoma as a result of dissection of coronary artery.
Vascular calcification, long thought to result from passive degeneration, involves a complex, regulated process of biomineralization resembling osteogenesis. Evidence indicates that proteins controlling bone mineralization are also involved in the regulation of vascular calcification. Artery wall cells grown in culture are induced to become osteogenic by inflammatory and atherogenic stimuli. Furthermore, osteoclast-like cells are found in calcified atherosclerotic plaques, and active resorption of ectopic vascular calcification has been demonstrated. In general, soft tissue calcification arises in areas of chronic inflammation, possibly functioning as a barrier limiting the spread of the inflammatory stimulus. Atherosclerotic calcification may be one example of this process, in which oxidized lipids are the inflammatory stimulus. Calcification is widely used as a clinical indicator of atherosclerosis. It progresses nonlinearly with time, following a sigmoid-shaped curve. The relationship between calcification and clinical events likely relates to mechanical instability introduced by calcified plaque at its interface with softer, noncalcified plaque. In general, as calcification proceeds, interface surface area increases initially, but eventually decreases as plaques coalesce. This phenomenon may account for reports of less calcification in unstable plaque. Vascular calcification is exacerbated in certain clinical entities, including diabetes, menopause, and osteoporosis. Mechanisms linking them must be considered in clinical decisions. For example, treatments for osteoporosis may have unanticipated effects on vascular calcification; the converse also applies. Further understanding of processes governing vascular calcification may yield new therapeutic options for vascular disease.
The purpose of this study was to evaluate the feasibility of carotid artery revascularization using a new system for carotid stenting and distal embolic protection in 30 patients with severe carotid stenosis and high risk for carotid endarterectomy (Carotid Revascularization With ev3 Arterial Technology Evolution, or CREATE). Previous studies suggest that patients with carotid stenosis and serious comorbid cardiopulmonary and anatomic conditions are at high risk for carotid endarterectomy. All patients underwent percutaneous revascularization using the Protégé GPS self-expanding nitinol stent (ev3, Plymouth, MN) and the Spider distal embolic protection system (ev3). In-hospital and 30-day outcomes were analyzed. High-risk features included age > 75 years (63%), left ventricular ejection fraction < 35% (20%), and restenosis after prior carotid endarterectomy (53%). Procedural success was 100%. In-hospital complications included severe vasovagal reactions in six patients (20%) and a popliteal embolus in one patient (3.3%), treated by successful embolectomy. During 30 days of follow-up, two patients (6.6%) experienced minor neurological deficits, including transient expressive aphasia that resolved without therapy in one patient and homonymous hemianopsia due to contralateral posterior circulation stroke in one patient. This study supports the feasibility of percutaneous carotid artery revascularization with the Protégé GPS self-expanding stent and Spider distal embolic protection system, which will be evaluated in a large multicenter pivotal trial (CREATE Pivotal Trial).
The synthesis and properties of carbonated apatite materials have received considerable attention due to their importance for medical and dental applications. Such apatites closely resemble the mineral phase of bone, exhibiting superior osteoconductive and osteogenic properties. When formed at physiological temperature they present significant potential for bone repair and fracture fixation. The present study investigates the mechanical properties of a carbonated apatite cancellous bone cement. Flexural strength was measured in three and four point bending, and the fracture toughness and fatigue crack-growth behaviour was measured using chevron and disc-shaped compact tension specimens. The average flexural strength was found to be approximately 0.468 MPa, and the fracture toughness was approximately 0.14 MPa radical m. Fatigue crack-growth rates exhibited a power law dependence on the applied stress intensity range with a crack growth exponent m=17. The fatigue threshold value was found to be approximately 0.085 MPa radical m. The mechanical properties exhibited by the carbonated apatite were found to be similar to those of other brittle cellular foams. Toughness values and fatigue crack-growth thresholds were compared to other brittle foams, bone and ceramic materials. Implications for structural integrity and longer term reliability are discussed.
Carotid endarterectomy is more effective than medical management in the prevention of stroke in patients with severe symptomatic or asymptomatic atherosclerotic carotid-artery stenosis. Stenting with the use of an emboli-protection device is a less invasive revascularization strategy than endarterectomy in carotid-artery disease.
We conducted a randomized trial comparing carotid-artery stenting with the use of an emboli-protection device to endarterectomy in 334 patients with coexisting conditions that potentially increased the risk posed by endarterectomy and who had either a symptomatic carotid-artery stenosis of at least 50 percent of the luminal diameter or an asymptomatic stenosis of at least 80 percent. The primary end point of the study was the cumulative incidence of a major cardiovascular event at 1 year--a composite of death, stroke, or myocardial infarction within 30 days after the intervention or death or ipsilateral stroke between 31 days and 1 year. The study was designed to test the hypothesis that the less invasive strategy, stenting, was not inferior to endarterectomy.
The primary end point occurred in 20 patients randomly assigned to undergo carotid-artery stenting with an emboli-protection device (cumulative incidence, 12.2 percent) and in 32 patients randomly assigned to undergo endarterectomy (cumulative incidence, 20.1 percent; absolute difference, -7.9 percentage points; 95 percent confidence interval, -16.4 to 0.7 percentage points; P=0.004 for noninferiority, and P=0.053 for superiority). At one year, carotid revascularization was repeated in fewer patients who had received stents than in those who had undergone endarterectomy (cumulative incidence, 0.6 percent vs. 4.3 percent; P=0.04).
Among patients with severe carotid-artery stenosis and coexisting conditions, carotid stenting with the use of an emboli-protection device is not inferior to carotid endarterectomy.
Balloon angioplasty of a bifurcation lesion is associated with lower rates of success and higher rates of complications than such treatment of lesions of most other morphologies. To date, the best device or procedure for bifurcation lesions has not been determined. The aim of this study was to compare the immediate and 3-month follow-up outcome of cutting balloon angioplasty (CBA) versus conventional balloon angioplasty (PTCA) for the treatment of bifurcation lesions. We treated 87 consecutive bifurcation lesions with CBA (n = 50) or PTCA (n = 37). Paired angiograms were analyzed by quantitative angiography, and angiographic follow-up was achieved for 93% of the lesions. The procedural success was 92% in the CBA group and 76% in the PTCA group (P < 0.05). Major in-hospital complications occurred in two lesions in the CBA group and six in the PTCA group (P = 0.05). The incidence of bail-out stenting in the CBA group was lower than in the conventional PTCA (8% vs 24%, P < 0.05). At the 3-month follow-up, the restenosis rate was 40% in the CBA group versus 67% in the PTCA group (P < 0.05). Clinical events during follow-up did not differ between the two groups. In conclusion, in comparison with PTCA, procedural success was greater and the restenosis rate lower with CBA. The results of this study support the use of the cutting balloon as optimal treatment for bifurcation lesions.
Unrecognized calcification is a cause of stent underexpansion which significantly increases the subsequent risks of restenosis and/or stent thrombosis. We describe the use of cutting balloon inflation within the implanted stent which overcame calcific restraint unresponsive to high pressure inflations with non-compliant balloons.
This work concerns with the implementation of a new stress-driven remodeling model for simulating the overall structure and mechanical behavior of a human carotid bifurcation. By means of an iterative finite element based procedure collagen fiber direction and maximal principal stresses are computed. We find that the predicted fibers' architecture at the cylindrical branches and at the apex of the bifurcation correlates well with histological observations. Some insights about the mechanical response of the sinus bulb and the bifurcation apex are revealed and discussed. The results are compared with other, isotropic and orthotropic, models available in the literature.